Separating ions in an ion trap

ABSTRACT

A method is disclosed comprising: trapping ions in an ion trap (40); applying a first force on the ions within the ion trap in a first direction, said force having a magnitude that is dependent upon the value of a physicochemical property of the ions; applying a second force on these ions in the opposite direction so that the ions separate according to the physicochemical property value as a result of the first and second forces; and then pulsing or driving ions out of one or more regions of the ion trap.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.17/090,073, filed Nov. 5, 2020, which is a continuation of U.S. patentapplication Ser. No. 15/568,601, filed Oct. 23, 2017, now U.S. Pat. No.10,861,687, which is a U.S. National Stage Application of InternationalApplication No. PCT/GB2016/051159, filed Apr. 25, 2016, which claimspriority from and the benefit of United Kingdom patent application No.1506909.9, filed Apr. 23, 2015, United Kingdom patent application No.1506906.5, filed Apr. 23, 2015, and United Kingdom patent applicationNo. 1506908.1, filed Apr. 23, 2015. The entire contents of each of theseapplications are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to mass and/or ion mobilityspectrometers and methods of mass and/or ion mobility spectrometry.Embodiments of the invention relate to an ion filter for filtering ionsaccording to a physicochemical property, a method and apparatus forimproving the resolution of ion mobility measurements, and a method andapparatus for improving the duty cycle of a discontinuous ion analysersuch as a time of flight (ToF) mass analyser.

BACKGROUND TO THE PRESENT INVENTION

A first set of embodiments of the present invention relate to an ionfilter. There are many situations in mass spectrometry where a lowresolution or poor quality mass to charge ratio filter is desired. Forexample, a low pass mass filter may be used to limit the range of massto charge ratios entering a Time of Flight (ToF) mass analyser so as toremove the effect of so called “wrap around”. Also, high pass massfilters (sometimes called the low mass cut-off filters) are often usedto clean up the parent and daughter ion data in MS^(e) “shotgun”experiments, i.e. experiments that periodically fragment parent ions andalternate between a parent ion analysis mode and a daughter ion analysismode. However, it is desired to provide an improved method of filteringions and an improved ion filter.

A second set of embodiments of the present invention relate to improvingthe resolution of ion mobility measurements. The maximum resolution of adrift time ion mobility separator (IMS) is proportional to the squareroot of the length of the drift path and the electrical field. Forexample, an increase of a factor of four is required in either parameterto gain an increase in resolution of a factor of two. It is desired toprovide an improved method of ion mobility separation and an IMS devicehaving an improved resolution.

A third set of embodiments of the present invention relate to improvingthe duty cycle of a discontinuous ion analyser. It is known to massselectively eject ions from an ion trap into a pusher region of a timeof flight (ToF) mass analyser so as to time focus a given range of massto charge ratios within the pusher and hence increase the duty cycle ofthe analyser. It is also known to use an ion mobility separator totemporally separate ions upstream of a ToF mass analyser, and thensynchronise the pusher of the ToF analyser with the arrival times of theions from the ion mobility separator. However, this method is generallyonly suitable for use with ions of a single charge state, as the ionmobility separation results in the temporal separation of ions ofdifferent charge states. It is also known to release ions from a small,low resolution TOF region into a travelling wave ion guide. The velocityof the travelling wave along the ion guide is controlled such that therequired mass ranges may be separated temporally and introduced into thepusher region of a TOF mass analyser so as to increase the duty cycle ofthe mass analyser. However, the velocity requirements for the travellingwave may result in significant fragmentation of ions at low mass tocharge ratios. It is desired to provide and improved method andapparatus for improving the duty cycle of a discontinuous ion analysersuch as a time of flight (ToF) mass analyser.

SUMMARY

From a first aspect the present invention provides a method of filteringions according to at least one physicochemical property, comprising:

trapping ions in an ion trap; and then

spatially separating the ions within the ion trap according to said atleast one physicochemical property so that ions become distributedwithin the ion trap according a known, determined or estimatedphysicochemical property distribution so that ions having differentvalues of said physicochemical property are trapped in different regionsof the ion trap;

selecting a desired first value, or first range of values, of saidphysicochemical property for first ions desired to be ejected from theion trap;

determining a first region of the ion trap in which said first ions arelocated from said known, determined or estimated physicochemicalproperty distribution; and then

driving or pulsing first ions trapped in said region out of the iontrap.

The present invention enables one to select the physicochemical propertyvalues of the ions that are driven out of the ion trap at said any onetime, thereby filtering the ions. The present invention also alleviatesspace-charge effects since the ions are distributed in the ion trapaccording to the physicochemical property.

WO 2005/106922 discloses a device for mass selectively ejecting ions byapplying opposing forces to the ions using DC and AC electric fields andthen varying the forces such that ions are ejected in order of mass tocharge ratio. However, according to this technique, the physicochemicalproperty distribution along the device is not known, determined orestimated. Accordingly, this technique does not determine the region inwhich ions having a selected value, or range of values, of thephysicochemical property are located based on a known, determined orestimated physicochemical property distribution, and then driving orpulsing ions trapped in this region out of the ion trap. Rather, in WO'922 there is no step of determining the location of the region in whichions desired to be ejected are located. This is because the ions aremass selectively scanned out of the device and so the ions ejected atany given time are always located adjacent the exit of the device. Thesedifferences arise because, in contrast to the embodiments of the presentinvention, the device in WO '922 does not filter ions so as toselectively transmit only ions of interest. Rather, all ions are scannedout of the device in WO '922.

US 2002/0070338 discloses separating ions according to ion mobility,halting the ion mobility separation and then raising a series ofpotential wells along the length of the device so as to lock in the ionmobility separation. The ions are then sequentially ejected by openingthe potential wells in sequence, starting at the exit end of the device.However, according to this technique the ions are not spatiallyseparated after being trapped in an ion trap. Also, the physicochemicalproperty distribution along the device is also not known, determined orestimated. Consequently, this technique does not determine the region inwhich ions having a selected value, or range of values, of thephysicochemical property are located based on a known, determined orestimated physicochemical property distribution, and then driving orpulsing ions trapped in this region out of the ion trap. Rather, inUS'338 the ions are always released from the trapping region at the exitof the device.

According to the method of said first aspect, ions trapped in the otherof said different trapping regions may remain trapped in those regionsduring said driving or pulsing of said first ions out of the ion trap.

For example, where the ion trap has a longitudinal axis and the ions aredistributed along the axis according to the physicochemical propertyvalues, the other ions may remain trapped at their respective axialpositions whilst the first ions are driven or pulsed out of the ion trapand, optionally, until said other ions are driven or pulsed out of theion trap.

A voltage supply may apply voltages to the ion trap so as to cause theions to remain trapped in their respective trapping regions during saiddriving or pulsing of said first ions out of the ion trap.

The method may comprise selecting a desired value, or range of values,of said physicochemical property for second ions desired to be ejectedfrom the ion trap; determining a second different region of the ion trapin which said second ions are located from said known, determined orestimated physicochemical property distribution; and then driving orpulsing the second ions trapped in said second region out of the iontrap.

The method of ejecting may be repeated for driving or pulsing third,fourth or additional groups of ions out of respective third, fourth oradditional regions of the ion trap.

The different groups of ions may be ejected from the ion trap at adifferent times from each other.

The method may comprise driving or pulsing ions trapped in only one ofsaid different regions out of the ion trap at any one time.

Accordingly, said step of spatially separating the ions may cause ionshaving the first value, or first range of values, for saidphysicochemical property to be trapped in the first region and ionshaving a second value, or second range of values, for saidphysicochemical property to be trapped in a second of said differentregions; and said step of driving or pulsing ions may drive or pulseonly said ions having the first value, or first range of values, forsaid physicochemical property out of the ion trap, at a first time.

The method may comprise driving or pulsing only said ions having thesecond value, or second range of values, for said physicochemicalproperty out of the ion trap, at a second later time.

The method may further comprise performing one or more further cycle ofoperation, wherein each cycle comprises: driving or pulsing trapped ionsout of one of said regions of the ion trap, whilst retaining other ionstrapped in other regions of the ion trap; wherein for each subsequentcycle of operation, ions are driven or pulsed out of a different regionof the ion trap from the previous cycles of operation.

For each subsequent cycle of operation, ions may be driven or pulsed outof the ion trap from a trapping region that is further away from theexit of the ion trap than the region from which ions were driven out inthe previous cycle of operation.

The ion trap may comprise an elongated ion trapping volume, and ionshaving said different values of said physicochemical property may betrapped in different regions along the longitudinal axis of the iontrap.

The ions having said different values of said physicochemical propertymay be trapped in the ion trap at different distances from the exit ofthe ion trap prior to being driven out of the ion trap from said exit.

The ion trap may have a longitudinal axis and said region from which theions are driven or pulsed out of may not be a region adjacent an exit ata longitudinal end of the ion trap.

The ions may be spatially separated within the ion trap according to theat least one physicochemical property so that the ions are dispersedalong the ion trap according to their physicochemical property valueswithout the spatially separated trapped ions being separated bypotential barriers.

The step of spatially separating the ions may not therefore comprisearranging a potential barrier, such as a DC potential barrier, betweenthe ions of different physicochemical property values. In this context,such a potential barrier is intended to mean a discrete barrier or well,rather than a potential gradient.

The ion trap may comprise an elongated ion guide having a plurality ofelectrodes arranged along its longitudinal axis. This allows one or morevoltage supply to apply different AC and/or DC voltages to differentaxial locations of the ion trap, for example, in order to radiallyconfine the ions and/or generate the DC gradient and/or generate thepseudo-potential and/or generate the travelling potential describedherein.

The ion trap may comprise a plurality of apertured electrodes withinwhich the ions are trapped by application or AC and/or DC voltages tothe electrode. For example, the ion trap may comprise a stacked ring ionguide or an ion tunnel ion guide. Less preferably, the ion trap maycomprise one or more multipole rod sets.

The ion trap may comprise geometries of electrodes other than thosedescribed above.

The step of separating the ions may cause the ions to be arranged inorder of the physicochemical property within the ion trap, either in amanner wherein the value increases or decreases in a direction towardsthe exit of the ion trap.

The ions of different physicochemical property values may be spatiallyseparated over a length of ≥x mm within the ion trap, wherein x isselected from the group consisting of: 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5,5, 6, 7, 8, 9, and 10.

The step of spatially separating the ions may comprise applying a firstforce on the ions within the ion trap in a first direction, said forcehaving a magnitude that is dependent upon the value of said at least onephysicochemical property of the ions; and applying a second force onthese ions in the opposite direction; optionally wherein the magnitudeof said second force is not dependent upon the value of said at leastone physicochemical property of the ions.

Optionally, said first and second forces are counterbalanced atdifferent locations within the ion trap for ions having differentphysicochemical property values, such that different ions are trapped atsaid different regions.

The ion trap comprises one or more electrodes and said method maycomprise generating said first force by applying AC or RF potentials tosaid electrodes so as to generate a pseudo-potential electric field thaturges ions in the first direction.

The ion trap comprises one or more electrodes and said method maycomprise generating said second force by applying one or more DCpotentials to said one or more electrodes so as to generate a DC voltageor DC voltage gradient that urges ions in the second direction; and/or agas flow may be provided through the ion trap so as to generate saidsecond force.

When said step of spatially separating the ions comprises separating theions according to more than one physicochemical property, the ions areseparated so that ions having different combinations of values for saidmore than one physicochemical property are trapped in different regionswithin the ion trap.

The step of driving or pulsing trapped ions out of a region of the iontrap may comprise varying an electrical potential along the trappingregion that ions are being driven or pulsed out of; and/or travelling anelectric potential along at least a portion of the ion trap so as todrive the ions out of the ion trap.

The method may comprise varying the electrical potential profile alongthe first region when driving or pulsing ions out of the first regionand/or varying the electrical potential profile along a second differentregion when driving or pulsing ions out of the second region.

As described above, the method may comprise a series of cycles in whichions are driven out of different ones of said regions in successivecycles. In each cycle, ions may be driven out of the region of the iontrap by travelling an electric potential along at least a portion of theion trap.

The electric potential may be travelled along a first length of the iontrap in order to drive or pulse the first ions out of the first regionof the ion trap at a first time, and an electric potential may besubsequently travelled along a second length of the ion trap in order todrive second ions out of a second of said different regions of the iontrap at a second time.

The first and second lengths of the ion trap may be overlapping. Thefirst length may be shorter than the second length, and the secondlength may include at least part of the first length.

The first length may extend from a first location in the ion trap to theexit of the ion trap, whereas the second length extends from a secondlocation in the ion trap to the exit of the ion trap, wherein the secondlocation is further from the exit than the first location.

The electric potential may be travelled along third and further lengthsof the ion trap at subsequent times in order to drive ions out of thirdand further ones of said different regions of the ion trap. Preferably,the electric potential repeatedly travels from an upstream location ofthe ion trap towards the exit of the ion trap, wherein the upstreamlocation becomes progressively further upstream as time progresses.

Optionally, the electric potential(s) that is travelled along the iontrap is a DC potential barrier or well.

Ions driven or pulsed from regions that are not regions of interest maybe discarded or neutralised, whereas selected ions of interest may beonwardly transmitted for mass and/or ion mobility analysis.

The method comprises calculating or determining a correlation betweenthe physicochemical property values of the ions and their locationswithin the ion trap; selecting a value, or range of values, of saidphysicochemical property for ions desired to be ejected from the iontrap; using said correlation to select one of said different regions ofsaid ion trap in which ions having that physicochemical property value,or range of values, are trapped; and driving ions out of that selectedregion.

Ions of interest having the selected value, or range of values, of saidphysicochemical property may be ejected from the ion trap andtransmitted to an ion analyser, or ion storage device. For example, theion analyser may be a mass analyser or ion mobility analyser.

Unwanted ions having a value, or range of values, of saidphysicochemical property that are not of interest may be ejected orreleased from the ion trap and/or are discarded or neutralised.

For example, the ion trap may be operated as a high pass filter and ionstrapped in the ion trap having physicochemical property values below afirst threshold value may be ejected or released from the ion trap anddiscarded or neutralised.

Alternatively, the ion trap may be operated as a low pass filter andions trapped in the ion trap having physicochemical property valuesabove a second threshold value may be ejected or released from the iontrap and discarded or neutralised.

Alternatively, the ion trap may be operated as a band pass filter andions trapped in the ion trap having physicochemical property valuesbelow a first threshold value and above a second threshold value may beejected or released from the ion trap and discarded or neutralised.

The unwanted ions may be discarded by travelling a DC voltage along theportion of the ion trap in which these unwanted ions are trapped, so asto force these ions out of the ion trap. Less preferably, the iontrapping voltages may be removed from the regions of the ion trap inwhich these unwanted ions are stored, e.g. the radial confinementvoltages may be removed in these regions.

The method may comprise pulsing ions into the ion trap and thenperforming the step of separating the ions.

The ion trap may be an elongated ion trap and the step of ejecting ionsfrom at least some of said different regions of the ion trap may beperformed by axially ejecting the ions from said at least some of saiddifferent regions; or the ion trap may be an elongated ion trap and thestep of ejecting ions from at least some of said different regions ofthe ion trap may be performed by radially ejecting the ions from said atleast some of said different regions.

Accordingly, the ion trap may have a longitudinal axis and the ions maybe driven or pulsed out of a longitudinal end of the ion trap, or mayberadially driven or pulsed out of the ion trap.

Unwanted ions may be radially ejected and desired ions may be axiallyejected.

Alternatively, desired ions may be radially ejected and unwanted ionsmay be axially ejected.

Ions may be ejected from the ion trap in order of physicochemicalproperty value, or reverse order, to a downstream ion analyser; and theoperation of the ion analyser may be varied with time.

For example, the downstream ion analyser may be a resolving quadrupoleor other multipole in which the mass to charge ratios transmitted by thequadrupole or multipole is scanned with time. Ejecting the ions from theion trap in order of physicochemical property value, or reverse order,serves to increase the duty cycle of the scanned device.

It is also contemplated that the ions ejected from the ion trap may befragmented in a collision cell.

The at least one physicochemical property may be mass to charge ratioand/or ion mobility.

The present invention also provides a method of mass spectrometry or ionmobility spectrometry comprising filtering ions according to any of themethods described herein. The method may further comprise mass analysingor ion mobility analysing ions driven out of the ion trap.

The first aspect of the present invention also provides an ion filterfor filtering ions according to at least one physicochemical property,comprising:

an ion trap for trapping ions;

an ion separator for spatially separating the ions within the ion trapaccording to at least one physicochemical property;

an ion driving or pulsing device for driving or pulsing ions out of theion trap; and

a controller having a processor and electronic circuitry adapted andconfigured to:

control the ion trap so as to trap ions therein;

control the ion separator so as to spatially separate the ions withinthe ion trap according to said at least one physicochemical property sothat ions become distributed within the ion trap according a selectedphysicochemical property distribution so that ions having differentvalues of said physicochemical property are trapped in different regionsof the ion trap;

determine a first region of the ion trap in which ions having apreselected first value, or first range of values, of saidphysicochemical property are located based on said physicochemicalproperty distribution; and then

drive or pulse first ions trapped in said region out of the ion trap.

The ion filter may be configured to perform any of the methods describedherein. In particular, the controller may control electrical circuitryand at least one voltage supply so as to apply voltages to the filter soas to perform any of the methods described herein.

The present invention also provides a mass spectrometer or ion mobilityspectrometer comprising an ion filter as described herein. Thespectrometer may comprise a detector for detecting ions driven or pulsedout of the ion trap and/or a mass analyser or ion mobility analyser foranalysing ions driven out of the ion trap.

Although the physicochemical property distribution has been describedabove as a known, determined or estimated physicochemical propertydistribution, it is contemplated herein that the physicochemicalproperty distribution need not necessarily be known, determined orestimated. Accordingly, the step of selecting a desired first value (orfirst range of values) of said physicochemical property for first ionsdesired to be ejected from the ion trap, and the step of determining afirst region of the ion trap in which said first ions are located fromthe known, determined or estimated physicochemical property distributionneed not necessarily be performed.

Accordingly, from a second aspect the present invention provides amethod of filtering ions according to at least one physicochemicalproperty, comprising:

trapping ions in an ion trap;

spatially separating the ions within the ion trap according to said atleast one physicochemical property so that ions having different valuesof said physicochemical property are trapped in different regions of theion trap; and then

driving ions trapped in one of said different regions out of the iontrap, optionally wherein ions trapped in only one of said differentregions are driven out of the ion trap at any one time.

This technique enables one to select the physicochemical property valuesof the ions that are driven out of the ion trap at said any one time,e.g., by driving ions out of only one of said different regions. Thistechnique also alleviates space-charge effects since the ions aredistributed according to the physicochemical property value in the iontrap.

The method of second aspect may comprise any of the features describedin relation to the first aspect of the invention.

Optionally, whilst said step of driving ions is performed, other ionsremain trapped in the other region(s) of the ion trap.

Ions may be driven out of the ion trap by being pulsed out.

The step of spatially separating the ions may cause ions having a firstrange of values for said physicochemical property to be trapped in afirst of said different regions and ions having a second range of valuesfor said physicochemical property to be trapped in a second of saiddifferent regions; and the step of driving ions may drive only said ionshaving the first range of values for said physicochemical property outof the ion trap, at a first time.

The method may comprise driving only said ions having the second rangeof values for said physicochemical property out of the ion trap, at asecond later time.

The method may further comprise performing one or more further cycle ofoperation, wherein each cycle comprises: driving trapped ions out of oneof said regions of the ion trap, whilst retaining other ions trapped inother regions of the ion trap; wherein for each subsequent cycle ofoperation, ions are driven out of a different region of the ion trapfrom the previous cycles of operation.

For each subsequent cycle of operation, ions may be driven out of theion trap from a trapping region that is further away from the exit ofthe ion trap than the region from which ions were driven out in theprevious cycle of operation.

The ion trap may comprise an elongated ion trapping volume, and ionshaving said different values of said physicochemical property may betrapped in different regions along the longitudinal axis of the iontrap; and/or the ions having said different values of saidphysicochemical property may be trapped in the ion trap at differentdistances from the exit of the ion trap prior to being driven out of theion trap from said exit.

The ion trap may comprise an elongated ion guide having a plurality ofelectrodes arranged along its longitudinal axis. This allows differentAC and/or DC voltages to be applied at different axial locations of theion trap, for example, in order to radially confine the ions and/orgenerate the DC gradient and/or generate the pseudo-potential and/orgenerate the travelling potential described herein.

The ion trap may comprise a plurality of apertured electrodes withinwhich the ions are trapped by application or AC and/or DC voltages tothe electrode. For example, the ion trap may comprise a stacked ring ionguide or an ion tunnel ion guide. Less preferably, the ion trap maycomprise one or more multipole rod sets.

The ion trap may comprise geometries of electrodes other than thosedescribed above.

The step of separating the ions may cause the ions to be arranged inorder of the physicochemical property within the ion trap, either in amanner wherein the value increases or decreases in a direction towardsthe exit of the ion trap.

The step of spatially separating the ions may comprise applying a firstforce on the ions within the ion trap in a first direction, said forcehaving a magnitude that is dependent upon the value of said at least onephysicochemical property of the ions; and applying a second force onthese ions in the opposite direction. Optionally, the magnitude of saidsecond force is not dependent upon the value of said at least onephysicochemical property of the ions.

The first and second forces may be counterbalanced at differentlocations within the ion trap for ions having different physicochemicalproperty values, such that different ions are trapped at said differentregions.

The ion trap comprises one or more electrodes and said method maycomprise generating said first force by applying AC or RF potentials tosaid electrodes so as to generate a pseudo-potential electric field thaturges ions in the first direction.

The ion trap comprises one or more electrodes and the method maycomprise generating said second force by applying one or more DCpotentials to said one or more electrodes so as to generate a DC voltageor DC voltage gradient that urges ions in the second direction; and/or agas flow may be provided through the ion trap so as to generate saidsecond force.

When said step of spatially separating the ions comprises separating theions according to more than one physicochemical property, the ions areseparated so that ions having different combinations of values for saidmore than one physicochemical property are trapped in different regionswithin the ion trap.

The step of driving trapped ions out of a region of the ion trap maycomprise travelling an electric potential along at least a portion ofthe ion trap so as to drive the ions out of the ion trap.

As described above, the method may comprise a series of cycles in whichions are driven out of different ones of said regions in successivecycles. In each cycle, ions may be driven out of the region of the iontrap by travelling an electric potential along at least a portion of theion trap.

Said electric potential may be travelled along a first length of the iontrap in order to drive first ions out of a first of said differentregions of the ion trap at a first time, and an electric potential issubsequently travelled along a second length of the ion trap in order todrive second ions out of a second of said different regions of the iontrap at a second time.

The first and second lengths of the ion trap may be overlapping. Forexample, the first length may be shorter than the second length, and thesecond length may include the first length.

The first length may extend from a first location in the ion trap to theexit of the ion trap, whereas the second length extends from a secondlocation in the ion trap to the exit of the ion trap, wherein the secondlocation is further from the exit than the first location.

The electric potential may be travelled along third and further lengthsof the ion trap at subsequent times in order to drive ions out of thirdand further ones of said different regions of the ion trap. Optionally,the electric potential repeatedly travels from an upstream location ofthe ion trap towards the exit of the ion trap, wherein the upstreamlocation becomes progressively further upstream as time progresses.

Optionally, the electric potential(s) that is travelled along the iontrap is a DC potential barrier or well.

The method may comprise calculating or determining a correlation betweenthe physicochemical property values of the ions and their locationswithin the ion trap; selecting a value, or range of values, of saidphysicochemical property for ions desired to be ejected from the iontrap; using said correlation to select one of said different regions ofsaid ion trap in which ions having that physicochemical property value,or range of values, are trapped; and driving ions out of that selectedregion.

Ions of interest having a selected value, or range of values, of saidphysicochemical property may be ejected from the ion trap andtransmitted to an ion analyser, or ion storage device. For example, theion analyser may be a mass analyser or ion mobility analyser.

Unwanted ions having a value, or range of values, of saidphysicochemical property that are not of interest may be ejected orreleased from the ion trap and/or discarded or neutralised.

For example, the ion trap may be operated as a high pass filter and ionstrapped in the ion trap having physicochemical property values below afirst threshold value may be ejected or released from the ion trap anddiscarded or neutralised.

Alternatively, the ion trap may be operated as a low pass filter andions trapped in the ion trap having physicochemical property valuesabove a second threshold value may be ejected or released from the iontrap and discarded or neutralised.

Alternatively, the ion trap may be operated as a band pass filter andions trapped in the ion trap having physicochemical property valuesbelow a first threshold value and above a second threshold value may beejected or released from the ion trap and discarded or neutralised.

The unwanted ions may be discarded by travelling a DC voltage along theportion of the ion trap in which these unwanted ions are trapped, so asto force these ions out of the ion trap. Less preferably, the iontrapping voltages may be removed from the regions of the ion trap inwhich these unwanted ions are stored, e.g. the radial confinementvoltages may be removed in these regions.

The method may comprise pulsing ions into the ion trap and thenperforming the step of separating the ions.

The ion trap may be an elongated ion trap and the step of ejecting ionsfrom at least some of said different regions of the ion trap may beperformed by axially ejecting the ions from said at least some of saiddifferent regions; or the ion trap may be an elongated ion trap and thestep of ejecting ions from at least some of said different regions ofthe ion trap may be performed by radially ejecting the ions from said atleast some of said different regions.

Unwanted ions may be radially ejected and desired ions may be axiallyejected.

Alternatively, desired ions may be radially ejected and unwanted ionsmay be axially ejected.

Ions ejected from the ion trap may be ejected in order ofphysicochemical property value, or reverse order, to a downstream ionanalyser; and the operation of the ion analyser may be varied with time.For example, the downstream ion analyser may be a resolving quadrupoleor other multipole in which the mass to charge ratios transmitted by thequadrupole or multipole is scanned with time. Ejecting the ions from theion trap in order of physicochemical property value, or reverse order,serves to increase the duty cycle of the scanned device.

It is also contemplated that the ions ejected from the ion trap may befragmented in a collision cell.

The at least one physicochemical property may be mass to charge ratioand/or ion mobility.

The present invention also provides a method of mass spectrometry or ionmobility spectrometry comprising filtering ions according to any of themethods described herein. The method may further comprise mass analysingor ion mobility analysing ions driven out of the ion trap.

The second aspect of the invention also provides an ion filter forfiltering ions according to at least one physicochemical property,comprising:

an ion trap;

an ion separator;

an ion driving device; and

a controller configured to control the ion trap to trap ions therein;control the ion separator so as to spatially separate the ions withinthe ion trap according to said at least one physicochemical property sothat ions having different values of said physicochemical property aretrapped in different regions of the ion trap; and then to control theion driving device so as to drive ions trapped in only one of saiddifferent regions out of the ion trap at any one time.

The ion filter may be configured to perform any of the methods describedherein. For example, the controller may include a processor, electroniccircuitry and at least one voltage supply configured and adapted toperform the methods described herein.

The present invention also provides a mass spectrometer or ion mobilityspectrometer comprising an ion filter as described herein. Thespectrometer may comprise a mass analyser or ion mobility analyser foranalysing ions driven out of the ion trap.

From a third aspect the present invention provides a method of ionmobility spectrometry and/or mass spectrometry comprising:

trapping ions in an ion trapping region;

spatially separating the ions within the ion trapping region accordingto at least one physicochemical property;

pulsing the separated ions out of the ion trapping region and into anion mobility separator, wherein ions that have been separated from eachother in the spatially separating step are pulsed out of the iontrapping region and into the ion mobility separator in the same ionpulse; and

separating the ions pulsed into the ion mobility separator according toion mobility.

As the ions are separated within the ion trapping region, ions of anygiven physicochemical property value become confined within a relativelysmall region within the ion trapping region. As such, when the ions arepulsed into the ion mobility separator (IMS), the initial ion pulsewidth for an ion of any given physicochemical property value isrelatively narrow even if a relatively large ion trapping region isused. This enables a large population of ions to be injected into theIMS device without degrading the resolution of the device.

The method may comprise detecting the ions that exit the ion mobilityseparator so as to determine their ion mobilities.

The step of pulsing the ions out of the ion trapping region may comprisepulsing all ions out of the ion trapping region in a single pulse.

The step of spatially separating the ions may cause ions havingdifferent values of said physicochemical property, or different rangesof values of said physicochemical property, to be trapped at differentlocations within the ion trapping region; and/or ions having differentvalues of said physicochemical property, or different ranges of valuesof said physicochemical property, may be pulsed out of the ion trappingregion from different locations within the ion trapping region duringsaid pulsing step.

When said step of spatially separating the ions comprises separating theions according to more than one physicochemical property, the ions areseparated so that ions having different combinations of values for saidmore than one physicochemical property are trapped at differentlocations within the ion trapping region.

The ion trapping region may comprise a linear ion trap or the iontrapping region may be elongated; and ions may be spatially separatedalong the longitudinal axis of the ion trapping region during the stepof spatially separating the ions.

The method may comprise spatially separating the ions after all of theions to be pulsed into the ion mobility separator in said pulse havebeen accumulated; or spatially separating the ions whilst the ions arebeing accumulated in the ion trapping region.

The at least one physicochemical property may be mass to charge ratioand/or ion mobility.

The method may comprise performing a plurality of cycles of operation,wherein each cycle comprises the steps of: (i) receiving and trappingions in the ion trapping region; (ii) spatially separating the ionsaccording to the at least one physicochemical property within the iontrapping region; and (iii) pulsing the ions out of the ion trappingregion and into an ion mobility separator, wherein ions that have beenseparated from each other in step (ii) are pulsed out of the iontrapping region and into the ion mobility separator in the same ionpulse.

The step of spatially separating the ions may comprise applying a firstforce on the ions within the ion trapping region in a first direction,said force having a magnitude that is dependent upon the value of saidat least one physicochemical property of the ions; and applying a secondforce on these ions in the opposite direction. Optionally, the magnitudeof said second force is not dependent upon the value of said at leastone physicochemical property of the ions.

The first and second forces may be counterbalanced at differentlocations within the ion trapping region for ions having differentphysicochemical property values, such that different ions are trapped atsaid different locations.

The ion trapping region may comprise a plurality of electrodes and themethod may comprise generating said first force by applying AC or RFpotentials to said electrodes so as to generate a pseudo-potentialelectric field that urges ions in the first direction.

The ion trapping region may comprise one or more electrodes and themethod may comprise generating said second force by applying one or moreDC potentials to said one or more electrodes so as to generate a DCvoltage or DC voltage gradient that urges ions in the second direction.Alternatively, or additionally, a gas flow may be provided through theion trapping region so as to generate said second force.

Optionally, the ions having different physicochemical property values,or different ranges of physicochemical property values, are notseparated from each other in the ion trapping region by a potentialbarrier such as a DC potential barrier. In this context, the potentialbarrier is intended to mean a discrete barrier or well, rather than asubstantially continuous potential gradient.

The ion trapping region may be formed by an ion trapping devicecomprising a stacked ring ion guide, ion tunnel, or multipole rod setelectrode.

Voltages may be applied to the ion trapping device such that ions aretrapped within the ion trapping device in three dimensions.

The method may comprise travelling an electric potential along the ionmobility separator so as to drive ions out of the ion trapping regionand into the ion mobility separator during said pulsing step.Optionally, the electric potential may be travelled along the iontrapping region at a constant speed.

The third aspect of the present invention also provides an ion mobilityspectrometer and/or mass spectrometer comprising:

an ion trap for trapping ions;

a spatial separator for spatially separating the ions within the iontrap;

an ion mobility separator for separating ions according to their ionmobility;

a pulsing device for pulsing ions out of the ion trap; and

a controller arranged and adapted to control the spectrometer to:

-   -   operate the spatial separator so as to separate the ions within        the ion trap according to at least one physicochemical property;    -   pulse the separated ions out of the ion trap and into the ion        mobility separator, such that the ions that have been separated        from each other are pulsed out of the ion trap and into the ion        mobility separator in the same ion pulse; and    -   separate the ions in the ion mobility separator.

The spectrometer may comprise a detector for detecting the ions thatexit the ion mobility separator so as to determine their ion mobilities.

The ion trap may be a linear ion trap or an elongated ion trap; and thecontroller may be arranged and adapted to cause ions to be spatiallyseparated along the longitudinal axis of the ion trap.

The spectrometer may be arranged and adapted to perform any of themethods described herein.

Embodiments provide an improvement in ion mobility resolution (Ω/ΔΩ) fora given IMS geometry. Currently, the maximum resolution of an IMS deviceis proportional to the square root of the length of the drift path andthe electrical field. Therefore an increase of a factor of four isrequired in either parameter to gain an increase in resolution of afactor of two.

By spatially separating the ions in a trapping device prior to injectioninto the IMS device it is possible to increase the resolution by over afactor of 5. Additionally, space-charge effects are minimised during theinjection of ions into the IMS device.

From a fourth aspect the present invention provides a method of massspectrometry and/or ion mobility spectrometry comprising:

trapping ions in an ion trap; and then

spatially separating the ions within the ion trap according to at leastone physicochemical property so that ions having different values ofsaid physicochemical property are trapped in different regions of theion trap; and then

driving or pulsing first trapped ions out of a first region of the iontrap and into a discontinuous ion analyser at a first time, whilstretaining other ions trapped in the ion trap;

analysing said first ions in a first cycle of said discontinuous ionanalyser;

driving or pulsing second trapped ions out of a second, different regionof the ion trap and into the discontinuous ion analyser at a second,subsequent time; and

analysing said second ions in a different cycle of said discontinuousion analyser.

It will be appreciated that a discontinuous ion analyser is an ionanalyser that analyses ions in a sequence of cycles, rather thancontinuously. For example, a Time of Flight mass analyser is adiscontinuous ion analyser that receives ions in an ion extractionregion and periodically pulses them into the time of flight region to adetector for mass analysis. Each pulse to the detector is a separatecycle of analysis.

Conventional arrangements may store ions in an ion trap upstream of adiscontinuous ion analyser and then pulse all of the ions from the iontrap into the ion analyser in a single pulse. Using such an ion trap mayimprove the duty cycle of the instrument, for example, by converting acontinuous ion beam into a pulsed ion source. However, if the ions inthe ion trap have a relatively wide range of physicochemical propertyvalues then they may not all be able to be analysed in the same cycle bya discontinuous ion analyser, resulting in a lower duty cycle. Forexample, when a group of ions having a wide range of mass to chargeratios is pulsed into a ToF mass analyser, the ions of different mass tocharge ratio spread temporally such that not all of the ions are presentin the pusher region when the extraction pulse is applied. This leads toa lower duty cycle. Also, conventional methods of trapping ions upstreamof the ion analyser lead to detrimental space-charge effects.

The present invention enables a population of ions having a relativelybroad range of physicochemical property values (e.g. mass to chargeratios) to be stored in an ion trap and analysed in a discontinuousanalyser, whilst maintaining a high duty cycle. In particular, byseparating ions within the ion trap according to a physicochemicalproperty and driving ions out of the ion trap from different regions atdifferent times, the ion analyser receives ions having a relativelysmall range of physicochemical property values in each analysis cycle.The technique also has relatively low space-charge effects, as the ionsare spatially separated within the ion trap.

WO 2007/010272 discloses a mass selective ion trap that is synchronisedwith a scanned mass filter. Pseudo-potential corrugations may be formedalong the length of the ion trap and an axial field may be used to driveions against these corrugations. As ions of different mass to chargeratios experience different forces from the pseudo-potentialcorrugations, ions may be ejected in reverse order of mass to chargeratios by sweeping the RF potentials applied to the ion trap. Ions aretherefore mass selectively scanned out of the ion trap as a continuousstream. However, until the ions are ejected they remain trapped togetherand are not spatially separated within the ion trap according to aphysicochemical property so that ions having different values of thephysicochemical property are trapped in different regions of the iontrap. As such, the space-charge effects in WO'272 remain relativelyhigh. Also, the instrument is unable to eject pulses of ions from thedifferent regions of the ion trap in order to eject ions havingdifferent ranges of physicochemical property, since in WO'272 thedifferent ions are trapped together in the same trapping region.

EP 2065917 discloses a series of ion traps. Ions of different mass tocharge ratios may be ejected through a slot in an electrode of each iontrap at different times by scanning the trapping voltages. However, thisinstrument does not spatially separate the ions within a trap so thations of different values of a physicochemical property are trapped indifferent regions of the trap. Rather, it would seem that the differentions would intermix as they oscillate in the RF trapping fields. Also,the instrument does not analyse ions ejected from different trappingregions in different cycles of a discontinuous analyser. There wouldseem to be no need to pulse ions into a discontinuous analyser in theinstrument of EP'917 since a continuous detector may be used incombination with the extraction voltages to determine the mass to chargeratios of the ions. The concept described above of enhancing the dutycycle in a discontinuous analyser is not suggested in EP'917.

U.S. Pat. No. 5,206,506 discloses a plurality of ion guiding channels inwhich pseudo-potential wells are arranged that manipulate ions in anumber of ways. This instrument may lower the potential barrier betweenadjacent wells in order to separate ions according to mass to chargeratio, although the separated ions are not then pulsed into adiscontinuous ion analyser in different cycles of the analyser. Thisinstrument may also be used to mass selectively eject ions from apseudo-potential well at the end of an ion guiding channel, althoughthis technique is similar to the ion trap in EP 2065917 in thatdifferent ions are not trapped in different regions of the well andthere is no requirement to use a discontinuous analyser.

According to embodiments of the present invention, said step of drivingor pulsing second trapped ions out of the second region of the ion trapmay be performed whilst retaining other ions trapped in the ion trap.

The ions may be spatially separated within the ion trap according to theat least one physicochemical property so that the ions are dispersedalong the ion trap according to their physicochemical property valueswithout the spatially separated trapped ions being separated bypotential barriers. The step of spatially separating the ions may nottherefore comprise arranging a potential barrier, such as a DC potentialbarrier, between the ions of different physicochemical property values.In this context, such a potential barrier is intended to mean a discretebarrier or well, rather than a potential gradient.

Whilst the first and/or second trapped ions are driven or pulsed out ofthe first and/or second regions of the ion trap, the other trapped ionsmay be caused to remain trapped at their respective different trappingregions, optionally until said other trapped ions are driven or pulsedout of their respective trapping regions into the discontinuous ionanalyser.

Accordingly, whilst the first trapped ions are driven or pulsed out ofthe first region of the ion trap, the second trapped ions may be causedto remain in said second region until the second trapped ions are drivenor pulsed out of the second region into the discontinuous ion analyserat the second time.

The first region may be closer to the exit of the ion trap than thesecond region.

Although first and second trapped ions have been described as beingtrapped and then driven or pulsed out of first and second trappingregions, further groups of ions may also be trapped in further trappingregions and then driven or pulsed out of those further trapping regionsinto the ion analyser. Accordingly, the method may comprise performingone or more further cycle of operation, wherein each cycle comprises:driving or pulsing trapped ions out of a region of the ion trap and intothe discontinuous ion analyser, whilst retaining other ions trapped inthe ion trap, and analysing the ions driven or pulsed out of the iontrap in a cycle of said discontinuous ion analyser; wherein for eachsubsequent cycle of operation, ions are driven or pulsed out of adifferent region of the ion trap from the previous cycles of operation,and the ions that are driven or pulsed out of the ion trap are analysedin a different cycle of said discontinuous ion analyser.

For each subsequent cycle of operation, ions may be driven out of theion trap from a trapping region that is further away from the ionanalyser than the region from which ions were driven out in the previouscycle of operation (e.g. further from the exit of the ion trap).

Optionally, after said step of trapping the ions, ions are not admittedinto the ion trap until after said steps of driving said first andsecond ions out of the ion trap have been performed. Furthermore, ionsmay not be admitted into the ion trap until after said plurality ofcycles of operation have been performed.

The method may comprise spatially separating the ions only after all ofthe ions to be analysed in the ion analyser have been accumulated.Alternatively, the step of spatially separating the ions may beperformed whilst the ions are being accumulated in the ion trap.

The ion trap may comprise an elongated ion trapping volume, and ionshaving said different values of said physicochemical property may betrapped in different regions along the longitudinal axis of the iontrap. Alternatively, or additionally, the ions having said differentvalues of said physicochemical property may be trapped in the ion trapat different distances from an entrance to the ion analyser prior tobeing driven out of the ion trap.

The ion trap may comprise an elongated ion guide having a plurality ofelectrodes arranged along its longitudinal axis. This allows differentAC and/or DC voltages to be applied at different axial locations of theion trap, for example, in order to apply the DC gradient and/orpseudo-potential and/or travelling potential described herein.

The ion trap may comprise a plurality of apertured electrodes withinwhich the ions are trapped by application or AC and/or DC voltages tothe electrode. For example, the ion trap may comprise a stacked ring ionguide or an ion tunnel ion guide. Less preferably, the ion trap maycomprise one or more multipole rod sets.

The ion trap may comprise geometries of electrodes other than thosedescribed above.

The at least one physicochemical property may be mass to charge ratioand/or ion mobility.

Said step of spatially separating the ions may comprise applying a firstforce on the ions within the ion trap in a first direction, said forcehaving a magnitude that is dependent upon the value of said at least onephysicochemical property of the ions; and applying a second force onthese ions in the opposite direction. Optionally, the magnitude of saidsecond force is not dependent upon the value of said at least onephysicochemical property of the ions.

Said first and second forces may be counterbalanced at differentlocations within the ion trap for ions having different physicochemicalproperty values, such that different ions are trapped at said differentregions.

Said ion trap may comprise one or more electrodes and said method maycomprise generating said first force by applying AC or RF potentials tosaid electrodes so as to generate a pseudo-potential electric field thaturges ions in the first direction.

The ion trap may comprise one or more electrodes and said method maycomprise generating said second force by applying one or more DCpotentials to said one or more electrodes so as to generate a DC voltageor DC voltage gradient that urges ions in the second direction; and/or agas flow may be provided through the ion trap so as to generate saidsecond force.

When said step of spatially separating the ions comprises separating theions according to more than one physicochemical property, the ions maybe separated so that ions having different combinations of values forsaid more than one physicochemical property are trapped at differentlocations within the ion trapping region.

Each of the steps of driving or pulsing trapped ions out of a region ofthe ion trap and into a discontinuous ion analyser, whilst retainingother ions trapped in the ion trap, may comprise travelling an electricpotential along at least a portion of the ion trap so as to drive theions out of the ion trap.

The electric potential may be travelled along a first length of the iontrap in order to drive said first ions out of the ion trap, and saidelectric potential may be subsequently travelled along a second,different length of the ion trap in order to drive said second ions outof the ion trap.

The first and second lengths of the ion trap may be overlapping. Thefirst length may be shorter than the second length, and the secondlength may include at least part of the first length.

The first length may extend from a first location in the ion trap to theexit of the ion trap, whereas the second length may extend from a secondlocation in the ion trap to the exit of the ion trap, wherein the secondlocation is further from the exit than the first location.

The electric potential may be travelled along third and further lengthsof the ion trap in order to drive ions out of the ion trap in the one ormore further cycles of operation. Optionally, in each cycle of operationthe electric potential travels from an upstream location of the ionguide towards the exit of the ion guide, and wherein the upstreamlocation becomes progressively further upstream in subsequent cycles ofoperation.

The electric potential that is travelled along the ion guide may be a DCpotential barrier or well.

Rather than using a travelling potential to drive ions out of the iontrap in each cycle of operation, one or both of the opposing forces onthe ions may be varied with time such that the resulting overall forcecauses ions to exit the ion guide and enter the discontinuous ionanalyser in each cycle of operation. For example, the DC gradient, gasflow rate, or pseudo-potential may be changed to eject different ions inthe different cycles of operation.

The discontinuous ion analyser may be a time of flight mass analyser, apulsed ion mobility analyser, or an Orbitrap® mass analyser.

The ion analyser may be an orthogonal acceleration time of flight massanalyser. However, the ion analyser may be a linear acceleration time offlight mass analyser. The present invention is also applicable to othertypes of discontinuous ion analyser.

The method may comprise pulsing the ions into the ion trap before thestep of separating the ions.

Substantially all of the ions driven out of the ion trap from any giventrapping region may be analysed in a single cycle of the discontinuousion analyser.

Ions having different values, or different ranges of values, for said atleast one physicochemical property may be analysed in said ion analyserin different cycles.

The fourth aspect of the present invention also provides a massspectrometer and/or ion mobility spectrometer comprising:

an ion trap;

an ion separator device;

an ion driving device;

a discontinuous ion analyser; and

a controller arranged and configured to:

trap ions within the ion trap;

control the ion separator device so as to spatially separate the ionswithin the ion trap according to at least one physicochemical propertyso that ions having different values for said physicochemical propertyare trapped in different regions of the ion trap; and then

control the ion driving device so as to drive or pulse first trappedions out of a first region of the ion trap and into the discontinuousion analyser at a first time, whilst retaining other ions trapped in theion trap;

control the discontinuous ion analyser so as to analyse said first ionsin a first cycle of analysis;

control the ion driving device so as to drive or pulse second trappedions out of a second, different region of the ion trap and into thediscontinuous ion analyser at a second, subsequent time; and

control the discontinuous ion analyser so as to analyse said second ionsin a second cycle of said analysis.

The spectrometer may be arranged and configured to perform any one ofthe methods described herein.

For example, the ion driving device may be arranged and configured totravel an electric potential along at least a portion of the ion trap soas to drive or pulse ions out of the ion trap; and the controller may beconfigured to control the ion driving device such that an electricpotential is travelled along a first length of the ion trap in order todrive or pulse said first ions out of the ion trap, and an electricpotential is travelled along a second length of the ion trap in order todrive or pulse said second ions out of the ion trap.

The discontinuous ion analyser may be a time of flight mass analyser, ora pulsed ion mobility analyser.

Embodiments comprise pulsing ions into an ion trap, and then spatiallyseparating the trapped ions using a combination of opposing DC andpseudo-potential fields. After separation, ions may be extracted from aselected region of the ion trap by travelling a DC potential barrieralong the selected region to the exit of the ion trap, so as to urgeions out of the ion trap. The other ions remain trapped in the ion trap.The travelling potential therefore extracts ions from a given spatialrange and the ions may be conditioned before passing to the pusherregion of a ToF mass analyser. The pusher region pulses these ions intothe ToF region and mass analyses them. A travelling potential thensweeps ions out of a different region of the ion trap and into thepusher region of the ToF mass analyser. When these ions are within thepusher region they are pulsed into the ToF region and mass analysed. Theprocess of sweeping ions out of different regions of the ion trap andpulsing them into the ToF region is repeated.

Once ions are pulsed into the ion trap, a period of time is needed toallow the ions to spatially separate. A quantity of time is alsorequired for the ToF mass analysis itself. This time may be used, forexample, to analyse incoming ions with a different analyser, e.g. byfragmenting the ions and analysing them in an analytical ion trap.

From a fifth aspect, the present invention provides the ion trapdescribed herein itself. Accordingly, the present invention provides anion trap for spatially separating ions according to a physicochemicalproperty, wherein the ion trap comprises:

a plurality of electrodes;

at least one AC or RF voltage supply;

at least one DC voltage supply and/or a pump for pumping gas through theion trap; and

a controller and circuitry arranged and configured to:

-   -   control the at least one AC or RF voltage supply so as to apply        one or more AC or RF voltages to said electrodes so as to        generate a pseudo-potential electric field that urges ions in a        first direction;    -   control the at least one DC voltage supply so as to apply one or        more DC voltages to said electrodes so as to generate a DC        electric field that urges ions in a second direction opposite to        the first direction, and/or control the pump so as pump gas        through the ion trap so as to urge ions in a second direction        opposite to the first direction;    -   control the DC voltage supply and/or pump and/or AC/RF voltage        supply so as to pulse or drive ions out of one or more regions        of the ion trap.

The ion trap may comprise any of the features described herein, e.g., asdescribed above in relation to the other aspects.

For example, the ion trap may comprise an elongated ion trapping volume;and in use ions having different values of said physicochemical propertymay be trapped in different regions along the longitudinal axis of theion trap, and/or ions having different values of said physicochemicalproperty may be trapped in the ion trap at different distances from anexit of the ion trap.

The ion trap may have a longitudinal axis and said one or more regionsfrom which the ions are driven or pulsed from may not be a regionadjacent an exit at a longitudinal end of the ion trap.

The ions may be spatially separated within the ion trap according to thephysicochemical property so that the ions are dispersed along the iontrap according to their physicochemical property values without thespatially separated trapped ions being separated by potential barriers.

The present invention also provides a method of operating an ion trap asdescribed herein in order to separate and eject ions. Accordingly, thefifth aspect of the present invention provides a method comprising:

trapping ions in an ion trap;

applying a first force on the ions within the ion trap in a firstdirection, said force having a magnitude that is dependent upon thevalue of a physicochemical property of the ions;

applying a second force on these ions in the opposite direction so thatthe ions separate according to the physicochemical property value as aresult of the first and second forces; and then

pulsing or driving ions out of one or more regions of the ion trap.

The method of trapping and separating ions may comprise any of thefeatures described herein, e.g., in relation to the other aspectsdescribed above.

For example, the magnitude of said second force may not be dependentupon the value of said at least one physicochemical property of theions.

The ion trap may comprise one or more electrodes and the method maycomprise generating said first force by applying AC or RF potentials tosaid electrodes so as to generate a pseudo-potential electric field thaturges ions in the first direction.

The ion trap may comprise one or more electrodes and said method maycomprise generating said second force by applying one or more DCpotentials to said one or more electrodes so as to generate a DC voltageor DC voltage gradient that urges ions in the second direction; and/or agas flow may be provided through the ion trap so as to generate saidsecond force.

The step of driving or pulsing trapped ions out of a region of the iontrap may comprise varying an electrical potential along the trappingregion that ions are being driven or pulsed out of; and/or travelling anelectric potential along at least a portion of the ion trap so as todrive the ions out of the ion trap.

The method may comprise varying the electrical potential profile along afirst region of the ion trap when driving or pulsing ions out of thefirst region and/or varying the electrical potential profile along asecond different region of the ion trap when driving or pulsing ions outof the second region.

The ion trap may be an elongated ion trap and the step of ejecting ionsfrom at least some of said different regions of the ion trap may beperformed by axially ejecting the ions from said at least some of saiddifferent regions; or the ion trap may be an elongated ion trap and thestep of ejecting ions from at least some of said different regions ofthe ion trap may be performed by radially ejecting the ions from said atleast some of said different regions.

The at least one physicochemical property may be mass to charge ratioand/or ion mobility.

In the method, spectrometer or ion trap according to the variousembodiments of the present invention, the ions of differentphysicochemical property values may be spatially separated over a lengthof ≥x mm within the ion trap, wherein x is selected from the groupconsisting of: 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12,14, 16, 18, 20, 25, 30, 35, 40, 45 and 50.

Ions having any given value for said physicochemical property may bedistributed over ≤y mm within the ion trap, wherein y is selected fromthe group consisting of: 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 14.4, 1.6,1.8, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 9.

Any one of the above ranges for x mm may be combined with any one of theabove ranges for y mm. Both of these distances are measured along theaxis of separation (i.e. the z-direction). It is desired that the rangeof ions is separated over a relatively large distance x mm, but thations of any given value for said physicochemical property aredistributed over a relatively small distance y mm.

Optionally, the physicochemical property value may be mass to chargeratio, the ions may be separated such that they are dispersed over alength L in the ion trap, and the ratio of the range of mass to chargeratios, in Daltons, trapped in the ion trap over length L to the lengthL over which the ions are trapped, in mm, may be selected from the groupconsisting of: (i) 5-6; (ii) 6-7; (iii) 7-8; (iv) 8-9; (v) 9-10; (vi)10-11; (vii) 11-12; (viii) 12-13; (ix) 13-14; (x) 14-15; (xi) 15-16;(xii) 16-17; (xiii) 17-18; (xiv) 18-19; and (xv) 19-20.

The separation of the ions according to said physicochemical propertymay be preserved during ejection of the ions from the ion trap.

Features described in relation to any one of the aspects of the presentinvention may be used in combination with the method or apparatus of anyother of the aspects described herein.

The spectrometer described herein may comprise:

(a) an ion source selected from the group consisting of: (i) anElectrospray ionisation (“ESI”) ion source; (ii) an Atmospheric PressurePhoto Ionisation (“APPI”) ion source; (iii) an Atmospheric PressureChemical Ionisation (“APCI”) ion source; (iv) a Matrix Assisted LaserDesorption Ionisation (“MALDI”) ion source; (v) a Laser DesorptionIonisation (“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation(“API”) ion source; (vii) a Desorption Ionisation on Silicon (“DIOS”)ion source; (viii) an Electron Impact (“EI”) ion source; (ix) a ChemicalIonisation (“CI”) ion source; (x) a Field Ionisation (“FI”) ion source;(xi) a Field Desorption (“FD”) ion source; (xii) an Inductively CoupledPlasma (“ICP”) ion source; (xiii) a Fast Atom Bombardment (“FAB”) ionsource; (xiv) a Liquid Secondary Ion Mass Spectrometry (“LSIMS”) ionsource; (xv) a Desorption Electrospray Ionisation (“DESI”) ion source;(xvi) a Nickel-63 radioactive ion source; (xvii) an Atmospheric PressureMatrix Assisted Laser Desorption Ionisation ion source; (xviii) aThermospray ion source; (xix) an Atmospheric Sampling Glow DischargeIonisation (“ASGDI”) ion source; (xx) a Glow Discharge (“GD”) ionsource; (xxi) an Impactor ion source; (xxii) a Direct Analysis in RealTime (“DART”) ion source; (xxiii) a Laserspray Ionisation (“LSI”) ionsource; (xxiv) a Sonicspray Ionisation (“SSI”) ion source; (xxv) aMatrix Assisted Inlet Ionisation (“MAII”) ion source; (xxvi) a SolventAssisted Inlet Ionisation (“SAII”) ion source; (xxvii) a DesorptionElectrospray Ionisation (“DESI”) ion source; and (xxviii) a LaserAblation Electrospray Ionisation (“LAESI”) ion source; and/or

(b) one or more continuous or pulsed ion sources; and/or

(c) one or more ion guides; and/or

(d) one or more ion mobility separation devices and/or one or more FieldAsymmetric Ion Mobility Spectrometer devices; and/or

(e) one or more ion traps or one or more ion trapping regions; and/or

(f) one or more collision, fragmentation or reaction cells selected fromthe group consisting of: (i) a Collisional Induced Dissociation (“CID”)fragmentation device; (ii) a Surface Induced Dissociation (“SID”)fragmentation device; (iii) an Electron Transfer Dissociation (“ETD”)fragmentation device; (iv) an Electron Capture Dissociation (“ECD”)fragmentation device; (v) an Electron Collision or Impact Dissociationfragmentation device; (vi) a Photo Induced Dissociation (“PID”)fragmentation device; (vii) a Laser Induced Dissociation fragmentationdevice; (viii) an infrared radiation induced dissociation device; (ix)an ultraviolet radiation induced dissociation device; (x) anozzle-skimmer interface fragmentation device; (xi) an in-sourcefragmentation device; (xii) an in-source Collision Induced Dissociationfragmentation device; (xiii) a thermal or temperature sourcefragmentation device; (xiv) an electric field induced fragmentationdevice; (xv) a magnetic field induced fragmentation device; (xvi) anenzyme digestion or enzyme degradation fragmentation device; (xvii) anion-ion reaction fragmentation device; (xviii) an ion-molecule reactionfragmentation device; (xix) an ion-atom reaction fragmentation device;(xx) an ion-metastable ion reaction fragmentation device; (xxi) anion-metastable molecule reaction fragmentation device; (xxii) anion-metastable atom reaction fragmentation device; (xxiii) an ion-ionreaction device for reacting ions to form adduct or product ions; (xxiv)an ion-molecule reaction device for reacting ions to form adduct orproduct ions; (xxv) an ion-atom reaction device for reacting ions toform adduct or product ions; (xxvi) an ion-metastable ion reactiondevice for reacting ions to form adduct or product ions; (xxvii) anion-metastable molecule reaction device for reacting ions to form adductor product ions; (xxviii) an ion-metastable atom reaction device forreacting ions to form adduct or product ions; and (xxix) an ElectronIonisation Dissociation (“EID”) fragmentation device; and/or

(g) a mass analyser selected from the group consisting of: (i) aquadrupole mass analyser; (ii) a 2D or linear quadrupole mass analyser;(iii) a Paul or 3D quadrupole mass analyser; (iv) a Penning trap massanalyser; (v) an ion trap mass analyser; (vi) a magnetic sector massanalyser; (vii) Ion Cyclotron Resonance (“ICR”) mass analyser; (viii) aFourier Transform Ion Cyclotron Resonance (“FTICR”) mass analyser; (ix)an electrostatic mass analyser arranged to generate an electrostaticfield having a quadro-logarithmic potential distribution; (x) a FourierTransform electrostatic mass analyser; (xi) a Fourier Transform massanalyser; (xii) a Time of Flight mass analyser; (xiii) an orthogonalacceleration Time of Flight mass analyser; and (xiv) a linearacceleration Time of Flight mass analyser; and/or

(h) one or more energy analysers or electrostatic energy analysers;and/or

(i) one or more ion detectors; and/or

(j) one or more mass filters selected from the group consisting of: (i)a quadrupole mass filter; (ii) a 2D or linear quadrupole ion trap; (iii)a Paul or 3D quadrupole ion trap; (iv) a Penning ion trap; (v) an iontrap; (vi) a magnetic sector mass filter; (vii) a Time of Flight massfilter; and (viii) a Wien filter; and/or

(k) a device or ion gate for pulsing ions; and/or

(l) a device for converting a substantially continuous ion beam into apulsed ion beam.

The spectrometer may comprise an electrostatic ion trap or mass analyserthat employs inductive detection and time domain signal processing thatconverts time domain signals to mass to charge ratio domain signals orspectra. Said signal processing may include, but is not limited to,Fourier Transform, probabilistic analysis, filter diagonalisation,forward fitting or least squares fitting.

The spectrometer may comprise either:

(i) a C-trap and a mass analyser comprising an outer barrel-likeelectrode and a coaxial inner spindle-like electrode that form anelectrostatic field with a quadro-logarithmic potential distribution,wherein in a first mode of operation ions are transmitted to the C-trapand are then injected into the mass analyser and wherein in a secondmode of operation ions are transmitted to the C-trap and then to acollision cell or Electron Transfer Dissociation device wherein at leastsome ions are fragmented into fragment ions, and wherein the fragmentions are then transmitted to the C-trap before being injected into themass analyser; and/or

(ii) a stacked ring ion guide comprising a plurality of electrodes eachhaving an aperture through which ions are transmitted in use and whereinthe spacing of the electrodes increases along the length of the ionpath, and wherein the apertures in the electrodes in an upstream sectionof the ion guide have a first diameter and wherein the apertures in theelectrodes in a downstream section of the ion guide have a seconddiameter which is smaller than the first diameter, and wherein oppositephases of an AC or RF voltage are applied, in use, to successiveelectrodes.

The spectrometer may comprise a device arranged and adapted to supply anAC or RF voltage to the electrodes. The AC or RF voltage preferably hasan amplitude selected from the group consisting of: (i) <50 V peak topeak; (ii) 50-100 V peak to peak; (iii) 100-150 V peak to peak; (iv)150-200 V peak to peak; (v) 200-250 V peak to peak; (vi) 250-300 V peakto peak; (vii) 300-350 V peak to peak; (viii) 350-400 V peak to peak;(ix) 400-450 V peak to peak; (x) 450-500 V peak to peak; and (xi) >500 Vpeak to peak.

The AC or RF voltage preferably has a frequency selected from the groupconsisting of: (i) <100 kHz; (ii) 100-200 kHz; (iii) 200-300 kHz; (iv)300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5 MHz;(viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi) 3.0-3.5 MHz;(xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz; (xv) 5.0-5.5MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0 MHz; (xix)7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii) 8.5-9.0 MHz;(xxiii) 9.0-9.5 MHz; (xxiv) 9.5-10.0 MHz; and (xxv) >10.0 MHz.

The spectrometer may comprise a chromatography or other separationdevice upstream of an ion source. The chromatography separation devicemay comprise a liquid chromatography or gas chromatography device. Theseparation device may comprise: (i) a Capillary Electrophoresis (“CE”)separation device; (ii) a Capillary Electrochromatography (“CEC”)separation device; (iii) a substantially rigid ceramic-based multilayermicrofluidic substrate (“ceramic tile”) separation device; or (iv) asupercritical fluid chromatography separation device.

The ion guide may be maintained at a pressure selected from the groupconsisting of: (i) <0.0001 mbar; (ii) 0.0001-0.001 mbar; (iii)0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar;(vii) 10-100 mbar; (viii) 100-1000 mbar; and (ix) >1000 mbar.

Analyte ions may be subjected to Electron Transfer Dissociation (“ETD”)fragmentation in an Electron Transfer Dissociation fragmentation device.Analyte ions may be caused to interact with ETD reagent ions within anion guide or fragmentation device.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be described, byway of example only, and with reference to the accompanying drawings inwhich:

FIG. 1 shows a graph of the positions at which ions of different mass tocharge ratio may be trapped within the ion filter of a preferredembodiment of the present invention;

FIG. 2 shows the spatial width over which any given ion will be trappedin the ion filter device;

FIG. 3 shows the mass to charge ratios of the ions trapped in the filterdevice as a function of position in the filter;

FIG. 4 shows the range of mass to charge ratios of the ions trapped inthe filter device as a function of position in the filter;

FIG. 5 shows an embodiment of the present invention wherein ions areaxially ejected from the filter device;

FIG. 6 shows an embodiment of the present invention wherein ions areorthogonally ejected from the filter device;

FIG. 7A shows a schematic of part of a prior art ion mobilityspectrometer comprising an ion trap and an IMS device, and FIG. 7B showsa schematic of part of an ion mobility spectrometer according to anembodiment of the present invention comprising an ion trap and an IMSdevice;

FIG. 8 shows a graph of the DC voltage potential profile along the iontrap of FIG. 7B;

FIG. 9 shows a graph of the RF voltage potential profile along the iontrap of FIG. 7B;

FIG. 10 shows a graph of the position along the ion trap at which thetotal potential is minimum for ions of different mass to charge ratios;

FIG. 11 shows the spatial width over which any given ion will be trappedin the ion trap of FIG. 7B;

FIG. 12 shows the temporal spread over which an ion of any given mass tocharge ratio will be ejected from the ion trap;

FIG. 13 shows a plot of drift time through the IMS device of FIG. 7B asa function of mass to charge ratio;

FIG. 14 shows two plots of resolution R against mass to charge ratio ofthe ions for the instruments of FIGS. 7A and 7B;

FIG. 15 shows a schematic of part of a ToF mass spectrometer;

FIG. 16 shows the mass of ions analysed by the ToF mass analyser as afunction of the pulse number in the pusher sequence;

FIG. 17 shows the position along the ion trap from which ions are sweptout of, as a function of the pulse number in the pusher sequence;

FIG. 18 shows the length of the region of the ion trap from which ionsare extracted, as a function of the pulse number in the pusher sequence;and

FIG. 19 shows a schematic of an ion trap according to an embodiment ofthe invention.

DETAILED DESCRIPTION

Embodiments of the present invention provide an ion trap that separatesions within the ion trap according to a physicochemical property, e.g.,mass to charge ratio.

A first set of embodiments provide a method and apparatus for massfiltering ions by trapping the ions in an ion trap of an ion filteringdevice, spatially separating the ions within the ion trap according totheir mass to charge ratios, and then selectively ejecting ions from oneor more sections of the ion trap such that ions having only the desiredmass to charge ratios are onwardly transmitted.

A second set of embodiments provide a method and apparatus for improvingthe resolution of ion mobility measurements by trapping ions in an iontrap, spatially separating the ions within the ion trap according totheir mass to charge ratios, and then pulsing the separated ions into anion mobility separator (IMS) in a single pulse.

A third set of embodiments provide a method and apparatus for improvingthe analysis of ions in a discontinuous ion analyser by trapping ions inan ion trap, spatially separating the ions within the ion trap accordingto their mass to charge ratios, and then driving or pulsing ions out ofdifferent regions of the ion trap into the discontinuous ion analyser atdifferent times.

The embodiments described herein separate the ions within an ion trapaccording to mass to charge ratios. The ions may be spatially separatedwithin the ion trap using a combination of a pseudo-potential electricfield and a DC electric field. For example, the ion trap may comprise astacked ring ion guide (or other ion guide) and a controller and relatedelectronic circuitry may control a voltage supply to apply an axial DCvoltage V_(dc)(z) along the length of the ion trap having the followingprofile:

V _(dc)(z)=d ₁ z+d ₂ z ²  (equation 1)

where z is the distance from the end of the ion trap, and d₁ and d₂ arethe coefficients of the linear and quadratic terms.

Similarly, the controller and related electronic circuitry may control avoltage supply to apply RF voltages to the electrodes so that the RFvoltage function along the ion trap, V_(x)(z), is as follows:

V _(x)(z)=p ₁ z+p ₂ z ²  (equation 2)

Where p₁ and p₂ are the coefficients of the linear and quadratic terms.

This results in an axial pseudo-potential profile, V_(ps)(z,m), givenby:

$\begin{matrix}{{V_{ps}( {z,m} )} = \frac{{q( {\frac{d}{dz}\lbrack {V_{x}(z)} \rbrack} )}^{2}}{4Mm\omega^{2}}} & ( {{equation}3} )\end{matrix}$

where M is the atomic mass unit, m is the mass to charge ratio of agiven ion, and ω is the applied RF voltage frequency.

$\begin{matrix}{{{Let}{\alpha(\omega)}} = \frac{q}{4M\omega^{2}}} & ( {{equation}4} )\end{matrix}$

Therefore, the pseudo-potential generated along the ion trap is givenby:

$\begin{matrix}{{V_{ps}( {z,m} )} = \frac{{{\alpha(\omega)}\lbrack {p_{1} + {2p_{2}z}} \rbrack}^{2}}{m}} & ( {{equation}5} )\end{matrix}$

The total potential for a given mass to charge ratio m and distance zfrom the end of the ion trap, V_(tot), is simply the sum of V_(DC) andV_(ps), and is therefore given by:

$\begin{matrix}{V_{tot} = {{d_{1}z} + {d_{2}z^{2}} + \frac{{{\alpha(\omega)}\lbrack {p_{1} + {2p_{2}z}} \rbrack}^{2}}{m}}} & ( {{equation}6} )\end{matrix}$

Ions of any given mass to charge ratio m will be located at a distance zfrom the end of the ion trap, at a distance where V_(tot) is a minimumfor that mass. Differentiating equation 6 and solving for the minimagives equation 7 below:

$\begin{matrix}{z = {- \frac{1}{2}{\frac{d_{1}}{d_{2}}\lbrack \frac{{4{\alpha(\omega)}\frac{p_{1}p_{2}}{d_{1}}} + m}{{4{\alpha(\omega)}\frac{p_{2}^{2}}{d_{2}}} + m} \rbrack}}} & ( {{equation}7} )\end{matrix}$

This equation can be used to calculate the position z at which thepseudo-potential minimum for any given ion is located, and hence theposition at which that ion will remain trapped.

For example, the curvature C(m) of the minima may be calculated from thesecond differential with respect to z of V_(tot) in equation 6, giving:

$\begin{matrix}{{C(m)} = {{2d_{2}} + \frac{8p_{2}^{2}{\alpha(\omega)}}{m}}} & ( {{equation}8} )\end{matrix}$

As long as the value of C(m) is greater than zero then equation 7 givesthe position of the minimum at which ions of a given mass to chargeratio will be trapped.

By optimisation of the DC potential parameters, d₁ and d₂, and the RFpotential parameters, p₁ and p₂, it is possible to obtain reasonablevoltage levels and good spatial separation of the ions within the iontrap.

As described above, this ion trap may be used to separate ion accordingto a physicochemical property (e.g., mass to charge ratio) in the first,second and third sets of embodiments described herein.

Various embodiments of said first set of embodiments will now bedescribed, in which the ion trap is used in an ion filter whichselectively ejects ions from one or more sections of the ion trap sothat ions having only the desired values of a physicochemical property(e.g., mass to charge ratio) are onwardly transmitted.

As described above, with optimisation of the DC potential parameters, d₁and d₂, and the RF potential parameters, p₁ and p₂, it is possible toobtain reasonable voltage levels and good spatial separation of the ionswithin the ion trap. In embodiments described below the optimisation ofthe parameters assumes an ion trap length of 0.2 m and a distribution ofions in the trap for ions having a range of mass to charge ratios of 100to 2000 Da.

FIG. 1 shows a graph of the position z at which the total potentialV_(tot) is minimum as a function of ion mass to charge ratio, for ionsof mass to charge ratio m between 100 and 2000 Da and for optimisedvalues of d₁=−1254 and d₂=−2280 which give a maximum V_(dc)=−150 V; andp₁=−560.96 and p₂=−43519.8 which give a maximum V_(x)=400 V, ω=100 kHz.

The ions are cooled by a buffer or background gas in the ion trap andthey reach thermal energy. A worst case assumption would be that theresidual axial energy ΔV of the ions was approximately ten times thisvalue, say ΔV=0.25 eV. This assumption then allows the spatial widthΔz(m) along the z-direction of the ion trap that any given ion willreside within to be determined, i.e. +/−0.25 V from the centralpotential position.

The spatial width Δz(m) along the ion trap in the z-direction withinwhich ions of any given mass to charge ratio are trapped can bedetermined from the curvature C(m) given in equation 8 above, such that:

$\begin{matrix}{{\Delta{z(m)}} = \sqrt{\frac{8\Delta V}{C(m)}}} & ( {{equation}9} )\end{matrix}$

FIG. 2 shows this spatial width Δz(m) as a function of the mass tocharge ratio of the ions.

FIG. 3 shows the mass to charge ratios of the ions in the ion guide as afunction of the electrode number in the ion guide forming the ion trap,i.e. effectively as a function of the distance z along the ion trap. Itcan be seen that the mass to charge ratios of the ions trapped in theion trap increase along the length of the ion trap. It can therefore beseen that ions of different mass to charge ratios can be ejected fromthe ion trap by ejecting ions from different regions of the length ofthe ion trap.

FIG. 4 shows the range of mass to charge ratios that are nominallytrapped adjacent each electrode in the ion trap, as a function of theelectrode number in the ion trap, i.e. effectively as a function of thedistance z along the ion trap. This shows a decreasing mass range withincreasing distance z from the end of ion trap, with a maximum range ofapproximately 17 Da.

The above example uses the DC and RF voltage profiles set out inequations 1 and 2 in order to generate the illustrated mass to chargeratio profile along the ion trap. However, different, choices of DCand/or RF voltage profiles may be used to tailor the mass to chargeratio distribution along the ion trap. Also, the ions may be separatedwithin the ion trap such that they are arranged in order of increasingor decreasing mass to charge ratio by altering the arrangement of the DCand RF voltages applied the ion trap.

FIG. 5 shows a schematic of an embodiment that may be used as a highpass mass to charge ratio filter, mimicking a low mass to charge ratiocut-off device. The system comprises a source of ions 1 (e.g.electrospray, REIMS, DESI, etc.), an ion trap or ion accumulation device2 (e.g. SRIG trap), an ion guide filter 3 comprising an ion trap forseparating the ions according to mass to charge ratio (e.g., asdescribed above), an ion neutralising/destroying device 4 (e.g. pDRElens), and onward transmission ion optics or a mass analyser 5. Device 5may be a mass to charge ratio analyser, such as Time of Flight (ToF)mass analyser or Orbitrap® etc. Alternatively, device 5 may be a gasfilled ion guide that converts the pulsed beam received therein into apseudo-continuous ion beam.

In use, ions from ion source 1 are accumulated in the ion trap 2 and arethen pulsed into the ion filter 3. The ion filter 3 comprises an iontrap of the type described above for separating the ions. Opposingforces are applied to the ions in the ion trap so as to cause them toseparate within the filter 3 according to mass to charge ratio, asdescribed above. The ions are allowed a short period of time after beingpulsed into the filter 3 (typically a few milliseconds to a few tens ofmilliseconds) to cool, spatially separate and take up their equilibriumspatial positions. Ions having different mass to charge ratios becomearranged at different positions within the filter 3. For example, theion distribution may be the same as that shown in FIG. 3. In thisembodiment the ions are arranged in order of mass to charge ratio withinthe filter 3, with the lower mass ions arranged towards the exit of thefilter 3. The instrument in this embodiment acts as a high pass deviceand it is therefore desired to discard ions below a threshold mass tocharge ratio. In order to do this, a controller and associated circuitrycontrols a voltage supply so as to apply a DC voltage to the ion trap ofthe filter 3 that travels along the portion of the filter 3 in which theunwanted ions are stored so as to force these ions out of the filter 3.

The unwanted ions are swept out of the filter 3 and into the ionneutralising/destroying device 4, which at this point is activate andneutralises or destroys the unwanted ions. The ionneutralising/destroying device 4 may be adapted and configured toelectronically neutralise the ions. For example, the ionneutralising/destroying device 4 may comprise a controller andassociated electronic circuitry that control a voltage supply to apply avoltage to an electrode that causes the unwanted ions to be deflectedonto a surface that electrically neutralises them, e.g., so that theycannot be analysed by a downstream ion analyser. For example, the ionneutralising/destroying device 4 may deflect the ion onto an electrodethat electrically neutralises the ions. Alternatively, the ionneutralising/destroying device 4 may react the ions with ions ofopposite polarity so as to neutralise them. The neutralising device 4 isthen deactivated and the remaining, desired ions are swept out of thefilter 3 by travelling a DC voltage along the filter 3. As the ionneutralising/destroying device 4 has been deactivated, the desired ionsare transmitted therethrough to the device 5.

The ion neutralising/destroying device 4 may alternatively be replacedwith a device that simply discards the ions. For example, a devicecomprising a controller and associated electronic circuitry that controla voltage supply to apply a voltage to an electrode that causes theunwanted ions to ejected from the instrument, e.g., so that they cannotbe analysed by a downstream ion analyser, may be used.

As an alternative to separating and arranging the ions in the filter 3in the above manner, the ions could be separated in the filter 3 suchthat the higher mass to charge ratio ions are arranged towards the exitof the filter 3. As such, a DC voltage may be travelled along theportion of the filter 3 in which the desired ions are stored so as toforce these ions out of the filter 3. These desired ions may then beonwardly transmitted to device 5. Ions in the filter 3 having massesbelow the threshold value may be discarded, e.g. by subsequentlytransmitting them to the ion neutralising/destroying device 4 orejecting them from the instrument in the manners described above. Forexample, the controller may switch off the trapping voltages in thefilter 3 such that these unwanted ions are no longer trapped.

The instrument may alternatively be configured as a low pass filter. Forexample, the ions could be separated so as to be arranged in order ofmass to charge ratio within the ion filter, with the lower mass ionsarranged towards the exit of the filter 3. However, this embodiment is alow pass filter and so only ions below a threshold mass to charge ratioare desired. As such, a DC voltage may be travelled along the portion ofthe mass filter in which the desired ions are stored so as to forcethese ions out of the filter 3. These desired ions may then be onwardlytransmitted to device 5. Ions in the filter having masses above thethreshold value may be neutralised or discarded, for example, in themanners described above.

Alternatively, the ions could be separated so as to be arranged in orderof mass to charge ratio within the ion filter, with the higher mass ionsarranged towards the exit of the filter 3. In this embodiment, the a DCvoltage is travelled along the portion of the mass filter 3 in which theunwanted ions are stored so as to force these ions out of the filter 3.These unwanted ions are neutralised or discarded, e.g. in the mannersdescribed above. The desired ions may subsequently be swept out of thefilter 3 by a travelling DC potential and onwardly transmitted to device5.

Alternatively, the device may be operated as a band pass filter. In thisembodiment the ions are separated in the filter 3 in the same manner asdescribed above. It is desired to neutralise or discard ions below afirst threshold mass to charge ratio and to neutralise or discard ionsabove a second threshold value. If the ions are arranged in order ofmass such that the low mass to charge ratios are arranged toward theexit of the filter 3, then a DC voltage is travelled along the portionof the filter 3 in which the ions having masses below the firstthreshold are stored so as to force these ions out of the filter 3.These ions are then neutralised or discarded, e.g. in the mannersdescribed above. A DC voltage is then travelled along the portion of thefilter 3 in which the desired ions are stored, i.e. the ions havingmasses between the first and second threshold values. These desired ionsare swept out of the filter 3 and are onwardly transmitted to device 5.Ions in the filter 3 having masses above the second threshold value maythen be neutralised or discarded, e.g. in the manners described above.

Alternatively, the ions could be arranged in order of mass to chargeratio within the ion filter, with the higher mass ions arranged towardsthe exit of the filter 3. In this embodiment, a DC voltage is travelledalong the portion of the filter 3 in which the ions having masses abovethe second threshold are stored so as to force these ions out of thefilter 3. These unwanted ions are neutralised or discarded, e.g. in themanners described above. A DC voltage is then travelled along theportion of the filter 3 in which the desired ions are stored, i.e. theions having masses between the first and second threshold values. Thesedesired ions are swept out of the filter 3 and are onwardly transmittedto device 5. Ions in the filter 3 having mass to charge ratios below thefirst threshold value may then be neutralised or discarded, e.g. in themanners described above.

FIG. 6 shows a schematic of an instrument that is the same as that shownin FIG. 5, except wherein ions are orthogonally transferred from the ionfilter 3 into an adjacent device 6, rather than being furthertransmitted along the longitudinal axis of the instrument. As such, theion neutralising/destroying device 4 may be omitted and replaced by adevice 6 that has a controller and associated circuitry for controllinga voltage supply to apply voltages to the ion trap so as to orthogonallyejections from the filter 3. The device 6 may be, for example, an ionguide (such as a Stepwave® ion guide) that is conjoined with filter 3 sothat ions travelling along the longitudinal axis of filter 3 may beselectively radially ejected into device 6 so as to travel along thelongitudinal axis of the device 6.

The instrument may be operated in any of the modes described above inrelation to FIG. 5, except that when the ions have been separated alongthe length of the filter 3 the desired ions may be orthogonally ejectedfrom the filter 3 into the ion guide 6. This is in contrast to thearrangement of FIG. 5, wherein the desired ions are swept out of thefilter 3 along its longitudinal axis. According to the instrumentillustrated in FIG. 6, the ions received in device 6 may be onwardlytransmitted to device 5.

Alternatively, rather than transferring desired ions into device 6, onlyunwanted ions may be transferred into the adjacent device 6. The desiredions may then be transferred along the longitudinal axis of filter 3 toan ion analyser.

The instrument may be operated both in simple filter modes in which theinstrument may be operated in either low pass, high pass or band passmodes. Alternatively, the instrument may be operated in complex filtermodes. For example, the instrument may be operated multi-pass filtermodes in which ions are first trapped, separated and filtered accordingto a low pass, high pass or band pass mode in filter 3; and at leastsome of the desired ions transmitted by the filter 3 are subsequentlyreintroduced into the filter 3 and are trapped, separated and filteredagain according to a low pass, high pass or band pass mode.

It is contemplated that the desired ions may be transmitted in a mass tocharge ratio dependent manner to a downstream device whose operation isscanned with time. For example, the scanned device may be a resolvingquadrupole or other multipole in which the mass to charge ratiostransmitted by the quadrupole or multipole is scanned with time. Thiscoupling serves to increase the duty cycle of the scanned device.

Alternatively the separated ions may be fragmented or reacted in anactive collision cell and, for example, a SWATH type experiment may beconducted. For example, ions having selected mass to charge ratio rangesmay be transmitted as separate pulses from the filter 3 into an activecollision, fragmentation or reaction cell, where the pulse shape orseparation is maintained. The collision energy or the fragmentation orreaction rate may be alternated or switched between a high collision,fragmentation or reaction value in which substantial fragmentation orreaction of the ions is performed and a low collision, fragmentation orreaction value in which substantial fragmentation or reaction of theions is not performed. The precursor ions from the first of the modesmay be mass and/or ion mobility analysed and the fragment or productions from the second of the modes may be mass and/or ion mobilityanalysed. The fragment or product ions may be assigned to theirrespective precursor ions, e.g., based on the times that they are massand/or ion mobility analysed or based on their ion signal intensityprofile shapes.

Various embodiments of said second set of embodiments will now bedescribed, in which the ion trap is used to separate ions and then ejectthe separated ions into an ion mobility separator (IMS) in a singlepulse.

FIG. 7A shows a schematic arrangement of part of a prior art ionmobility spectrometer. The spectrometer comprises an ion trap 20arranged upstream of an IMS device 24. Ions are trapped in the ion trap20 prior to being pulsed into the IMS device 24. Prior to injection intothe IMS device 24, the ions are distributed substantially throughout theentire length of the ion trapping device 20 so as to maximise the ionstorage capacity.

Rokushika et al (Rokushika S, Hatano H, Baim M A, Hill H H, Anal Chem1985 (57) pp 1902-1907) showed that the resolution of an IMS device isdependent upon the temporal width of the ion injection pulse into thedevice and the diffusion broadening that occurs along the drift pathwithin the IMS device. The resolution of an IMS device can be describedthe following equation:

$\begin{matrix}{R = \frac{t}{\sqrt{\lbrack {W_{0}^{2} + W_{d}^{2}} \rbrack}}} & ( {{equation}10} )\end{matrix}$

where t is the drift time of the ion along the drift path, W₀ is theinitial ion pulse width, and W_(d) is the diffusion broadened peakwidth.

The diffusion broadened peak width W_(d) is given by:

$\begin{matrix}{W_{d} = \sqrt{\frac{16{\ln(2)}{kTt}^{2}}{qEL}}} & ( {{equation}11} )\end{matrix}$

where k is the Boltzmann constant, T is temperature, t is the drift timeof the ion along the drift path, q is the electronic charge, E is theelectric field in the drift region, and L is the length of the driftregion.

The prior art arrangement of providing an ion trap device 20 upstream ofthe IMS device 24 is advantageous in that it increases the ionpopulation that can be injected into the IMS device 24 at any one time.However, prior to injection, ions of any given mass to charge ratio aredistributed throughout the ion trap 20 and so the initial ion pulsewidth W₀ for ions of any given mass is relatively wide, resulting in arelatively low resolution for ion mobility measurement when the ions arepulsed into the IMS device.

The second set of embodiments of the present invention provide animprovement in measured ion mobility resolution through a reduction ofthe magnitude of W₀ for any given type of ion.

FIG. 7B shows a schematic arrangement of part of an ion mobilityspectrometer according to an embodiment of the present invention. Theinstrument is the same as that in FIG. 7A, except that it is configuredto spatially separate the ions in the ion trap 20 according to theirmass to charge ratio. In the illustrated example, ions of a first massare separated to one end of the ion trap 20 and ions of another mass areseparated towards the other end of the ion trap 20. Although only twogroups of ions 26,28 are shown, other groups of ions of different massto charge ratios may be separated and stored in groups that are arrangedbetween the two illustrated groups 26,28.

As the ions are separated within the ion trap 20, ions of any given massto charge ratio become confined within a relatively small region withinthe ion trap 20. As such, when the ions are injected into the IMS device24, the initial ion pulse width W₀ for ions of any given mass to chareratio is relatively narrow, even though a relatively large ion trap 20has been used. This enables a large population of ions to be injectedinto the IMS device 24 without degrading the resolution of the ionmobility spectrometer. The separated ions may be injected into the IMSdevice 24 together in the same pulse into the IMS device 24. Theinjection may be performed in a manner that maintains the separation ofthe ions, at least to some degree, during the injection.

As described above, ions may be spatially separated in the ion trap 24using a combination a pseudo-potential electric field and a DC electricfield. As also described above, with optimisation of the DC potentialparameters, d₁ and d₂, and the RF potential parameters, p₁ and p₂, it ispossible to obtain reasonable voltage levels and good spatial separationof the ions within the ion trap. In the embodiments below, optimisationof the parameters assumes an ion trap length of 0.1 m and a distributionof ions in the trap for ions having a range of mass to charge ratios of100 to 2000 Da.

FIG. 8 shows the DC voltage potential profile V_(dc)(z) along the iontrap 20 achieved using values of d₁=−1254, d₂=−2280, a maximumV_(dc)=−150 V, and ω=100 kHz.

FIG. 9 shows the RF voltage potential profile V_(x)(z) along the iontrap 20 achieved using parameters p₁=−560.96 and p₂=−43519.8 and amaximum V_(x)=400 V.

FIG. 10 shows a graph of the position z at which the total potentialV_(tot) is minimum as a function of ion mass to charge ratio, for ionsof mass to charge m between 100 and 2000 Da, and for the combinationvoltage profiles shown in FIGS. 8 and 9.

The ions are cooled by the buffer or background gas in the ion trap 20and they reach thermal energy. A worst case assumption would be that theresidual axial energy ΔV of the ions was ten times this value, sayapproximately ΔV=0.25 eV. This assumption then allows the spatial widthΔz(m) along the z-direction of the ion trap that any given ion willreside within to be determined from equation 9 above, i.e. +/−0.25 Vfrom the central potential position.

FIG. 11 shows this spatial width Δz(m) as a function of the mass tocharge ratio of the ions.

Once the ions have been separated in the ion trap 20, the separated ionsare injected into the IMS device 24. This may be performed by travellinga voltage along the ion trap 20. For example, a controller andassociated circuitry may control a voltage supply so as to apply one ormore voltage (e.g., a DC voltage) to the ion trap 20 that travels alongthe ion trap 20 so as to pulse ions from the ion trap 20 into the IMSdevice 24. The velocity v of the ions exiting the ion trap 20 may becontrolled, e.g., by setting or controlling the velocity of thetravelling voltage. For example, the velocity v is typically set to theorder of 300 m/s. Therefore, the spatial spread Δz of ions having anygiven mass to charge ratio may be mapped into a temporal spread Δt ofthese ions leaving the ion trap 20, wherein Δt=Δz/v.

FIG. 12 shows a plot of the temporal spread of the ions Δt as a functionof mass to charge ratios of the ions.

The drift time t in equation 11 above is dependent upon the mass tocharge ratio of the ions. The drift time t(m) may be calculated usingthe following equation:

$\begin{matrix}{{t(m)} = \frac{L_{d}}{E_{d}\lbrack {\frac{\sqrt{18\pi}q}{16\sqrt{kT}}\sqrt{\frac{1}{mM} + \frac{1}{m_{b}M}}\frac{{kT}1}{p{\Omega(m)}}} \rbrack}} & ( {{equation}12} )\end{matrix}$

where L_(d) is the length of the ion mobility drift tube, E_(d) is theelectric field along the drift tube, p is the pressure, m_(b) is themolecular mass of the buffer gas, and Ω (m) is the collisioncross-sectional area. For simplicity, only ions of single charge havebeen considered here.

The collision cross-sectional area Ω (m) may be estimated by thefollowing equation, which is based upon the molecular radii of the ionand buffer gas molecules:

$\begin{matrix}{{\Omega(m)} = {\prod\lbrack \frac{1.436( {\sqrt[3]{m} + \sqrt[3]{m_{b}}} )}{2} \rbrack}} & ( {{equation}13} )\end{matrix}$

FIG. 13 shows a plot of drift time Dt as a function of mass to chargeratio. This plot was obtained using the equation for t(m) above andsubstituting reasonable values for the operational parameters, whichwere an electric field along the drift tube E_(d) of 3 kV/m, a length ofthe ion mobility drift tube L_(d) of 1 m, a temperature T of 293 K, anda pressure p of 3 mbar nitrogen.

The parameter Δt is equivalent to the initial ion pulse width W₀ inequation 10 above. The diffusion broadened peak width W_(d) may becalculated using the estimated drift times t(m) from equation 13 above.Accordingly, the resolution R may be determined from equation 10 above.

FIG. 14 shows two plots of resolution R against mass to charge ratio ofthe ions. The lower plot corresponds to that of a prior art techniquethat does not spatially separate the ions in the ion trap 20 (i.e. usingthe instrument shown in FIG. 7A) and which gates ions into the IMSdevice 24 using a gate time of 250 μs. In other words, the initial ionpulse width W₀ is 250 μs. The upper plot corresponds to an embodiment ofthe present invention that spatially separates the ions in the ion trap20. FIG. 14 indicates that the embodiments of the present inventionprovide a significant increase in the resolution of the ion mobilityspectrometer over the prior art spectrometer. The enhancement inresolution increases with decreasing ion mobility drift time. For massto charge ratios up to 1000 Da, there is a greater than two foldenhancement in resolution. The embodiments allow ion mobilitymeasurements to be made with high resolution, even though a large iontrap 20 is utilised to inject a large ion population into the IMS device24 at any one time.

The embodiments introduce a mass to charge ratio dependent shift in themeasured drift time, since ions of different mass to charge ratios areseparated and stored in the ion trap 20 at different distances from theentrance to the IMS device 24. However, this may be easily taken care ofby calibration. In addition, the pre-separation may be ion mobilitydependent and may result in an increase in temporal separation.

The IMS device 24 may comprise a drift length having a static DC fieldarranged across it for forcing ions to separate within the IMS device 24according to ion mobility. Alternatively, an electric potential barriermay be travelled along the drift length of the IMS device 24 in order toforce the ions to separate according to ion mobility in the IMS device24.

Various embodiments of said third set of embodiments will now bedescribed, in which the ion trap is used to separate ions and then ejectseparated groups of ions into a discontinuous ion analyser at differenttimes.

FIG. 15 shows a schematic of part of a conventional Time of Flight (ToF)mass spectrometer. The apparatus comprises an ion trap 32 of length Z,an ion transfer region 34 of length L, and a pusher region 36 of anorthogonal acceleration time of flight (oa-ToF) mass analyser having alength ΔL.

In use, ions are trapped in the ion trap 32 and are pulsed into the iontransfer region 34. Ion optics in the transfer region 34 guide the ionsto the pusher region 36. The pusher region 36 pulses an orthogonalacceleration electric field such that the ions are acceleratedorthogonally from their flight path and into the time of flight regionof the ToF mass analyser. In order to achieve the optimum duty cycle ofthe oa-ToF spectrometer, all of the ions released from the trap 32 mustbe spatially located within the pusher region 36 when the orthogonalacceleration field is applied. The following calculations can be made todetermine the mass to charge ratios of the ions that would fulfil thiscondition.

The time of flight T₁ for an ion of mass to charge ratio m₁ to travelfrom the exit of the ion trap 32 (at z=0) to the end of the pusherregion 36 is as follows:

$\begin{matrix}{T_{1} = {\sqrt{\frac{{Mm}_{1}}{2{qVz}}}( {L + {\Delta L}} )}} & {{equation}(14)}\end{matrix}$

where M is the atomic mass unit, q is the electronic charge constant,V_(z) is the potential that the ion experiences on its journey throughthe ion transfer optics in the transfer region 34, and (L+ΔL) is thedistance from the exit of the ion trapping region 32 to the end of thepusher region 36.

The time of flight T₂ of a second ion of higher mass to charge ratio m₂to travel the distance L from the exit of the ion trapping region 32 (atz=0) to the entrance of the pusher region 36 is as follows:

$\begin{matrix}{T_{2} = {\sqrt{\frac{{Mm}_{2}}{2{qV}_{z}}}(L)}} & {{equation}(15)}\end{matrix}$

By setting time of flight T₁ to be equal to the time of flight T₂ onecan determine the mass to charge ratio m₂ of the ions that have reachedthe entrance to the pusher region 36 at the same time that ions of massto charge ratio m₁ have reached the exit of the pusher region 36. Thisresults in the following equation:

$\begin{matrix}{m_{2} = {( {1 + \frac{\Delta L}{L}} )^{2}m_{1}}} & {{equation}(16)}\end{matrix}$

In order to increase the duty cycle of the ToF mass analyser it isrequired that the pusher is presented with a restricted range of mass tocharge ratios, otherwise all of the ions will not be located within thepusher region 36 at the time that the orthogonal acceleration extractionpulse is applied. The required range of mass to charge ratios m_(i),m_(i-1) as a function of the sequential push number i, is as follows:

$\begin{matrix}{m_{i} = {{( {1 + \frac{\Delta L}{L}} )^{2}m_{i - 1}} = {( {1 + \frac{\Delta L}{L}} )^{2{({i - 1})}}m_{1}}}} & {{equation}(17)}\end{matrix}$

FIG. 16 shows the values of m_(i) as a function of the pulse number ifor an instrument having a typical ion transfer region 34 length L and atypical pusher region 36 length ΔL. In this example the ion transferregion length L is 0.13 m, the pusher region length ΔL is 0.033 m, andthe range of mass to charge ratios pulsed in the first pulse is m₁=100Da.

The third set of embodiments of the present invention provide animprovement over such conventional discontinuous ion analysers byspatially separating the ions according to a physicochemical property(e.g., mass to charge ratio) in an ion trap upstream of thediscontinuous ion analyser.

As described above, according to the embodiments of the presentinvention, ions may be spatially separated in the ion trap using acombination a pseudo-potential electric field and a DC electric field soas to provide the relationship in equation 7 above, from which can bedetermined the position z at which the pseudo-potential minimum for anygiven ion is located, and hence the position at which that ion willremain trapped.

As the ions are separated along the ion trap according to mass to chargeratio, ions may be swept out of the ion trap from different positionswithin the ion trap in order to eject different ranges of mass to chargeratio into the downstream ion analyser. In order to do this, acontroller and associated circuitry may control a voltage supply so asto apply a DC voltage to the ion trap that travels along the ion trap soas to eject the ions into the downstream ion analyser.

Substituting m_(i) from equation 17 above into equation 7, gives thedistance along the ion trap that must be swept out by the travellingvoltage in the i_(th) pulse. This distance z_(i) is given by thefollowing equation:

$\begin{matrix}{z_{i} = {- \frac{1}{2}{\frac{d_{1}}{d_{2}}\lbrack \frac{{4{\alpha(\omega)}\frac{p_{1}p_{2}}{d_{1}}} + {( {1 + \frac{\Delta L}{L}} )^{2{({i - 1})}}m_{1}}}{{4{\alpha(\omega)}\frac{p_{2}^{2}}{d_{2}}} + {( {1 + \frac{\Delta L}{L}} )^{2{({i - 1})}}m_{1}}} \rbrack}}} & ( {{equation}18} )\end{matrix}$

As described above, with optimisation of the DC potential parameters, d₁and d₂, and the RF potential parameters, p₁ and p₂, it is possible toobtain reasonable voltage levels and good spatial separation of the ionswithin the ion trap.

FIG. 17 shows the position z_(i) along the ion trap from which thetravelling voltage sweeps ions towards the exit of the ion trap (whereinthe exit is at z=0) as a function of push number i, for pushes i betweeni=1 and i=7. In this model, the length of the ion trapping device is 0.2m and ω=100 kHz. Optimised values for the DC voltage gave d₁=−2425 andd₂=−2280, with a maximum of −300 V and the RF voltage p₁=−270 andp₂=43272 and shows a maximum of approximately 400 V.

As can be seen from FIG. 17, the distance that the travelling voltagemust travel along the ion trap increases in subsequent push numbers.This enables ions from different depths within the ion trap to bereceived in the pusher region 36 of the ToF mass analyser when differentorthogonal acceleration pulses are applied. As ions having differentranges of mass to charge ratio are trapped at different depths in theion trap (i.e. different values of z), ions having different ranges ofmass to charge ratio are analysed in the different orthogonalacceleration pulses.

FIG. 18 shows the length Δz of the ion trap that both contains trappedions and from which ion are extracted, as a function of the ToF pushnumber i. It can be seen that the ions trapped over a small length (e.g.6 mm) of the ion trap are swept into the pusher region for the firstpush at i=1. The next sweep extracts ions trapped over a larger lengthof the ion trap, such that these ions are swept into the pusher regionfor the second push at i=2. It will be seen that subsequent sweepsextract ions that were trapped over progressively increasing lengths ofthe ions trap. FIG. 18 shows data that would cover a mass range between1 and approximately 2000 Da, requiring a minimum sweep of approximately6 mm of ion guide and thus is entirely possible with currenttechnologies.

The third set of embodiments of the invention enables ions having arelatively large range of mass to charge ratios to be trapped in the iontrap 32, without the ions being ejected from the ion trap 32 and intothe pusher region 36 in a manner that overfills the pusher region 36 atthe time the orthogonal acceleration extraction pulse is applied. Byspatially separating the ions within the ion trap, ions of any givenrange of mass to charge ratios become confined within a sub-region(which may be a relatively small region) of the ion trap. Differentranges of mass to charge ratios may then be swept out of the ion trapand into the mass analyser at different times by ejecting ions fromdifferent regions of the ion trap at different times.

FIG. 19 shows an embodiment of the ion trap 40 that may be used in thevarious embodiments described herein. The ion trap 40 may be a linearion trap and comprises a plurality of apertured electrodes 42. An AC orRF voltage supply 44 may apply AC or RF voltages to the electrodes 42 soas to radially confine ions within the ion trap 40. Opposite phases ofan AC or RF voltage may be applied to axially adjacent electrodes.Different AC or RF voltages (e.g., different magnitudes) may be appliedto different electrodes 42 along the ion trap 40 so as to generate afirst force on the ions in a first direction along the axial length ofthe ion trap 40. A DC voltage supply 46 may apply DC voltages to theelectrodes 42. Different DC voltages (e.g., different magnitudes) may beapplied to different electrodes 42 along the ion trap 40 so as togenerate a second force on the ions in a second direction along theaxial length of the ion trap 40, opposite to the first direction.Additionally, or alternatively, a pump 48 may be provided to generate agas flow through the ion trap 40 that generates a force on the ions inthe second direction.

A controller 50 is provided that comprises an ion separator. Thecontroller and ion separator contain a processor and electroniccircuitry that are configured to control the voltage supplies 44,46(and/or pump 48) so as to apply the voltages to the electrodes 42(and/or pump the gas through the ion trap 42) that cause the first andsecond forces to be generated on the ions. This causes the ions toseparate along the axial length of the ion trap 40 according to mass tocharge ratio, as described above.

The controller 50 also comprises an ion driving or pulsing circuit thatcontain a processor and electronic circuitry configured to control thevoltage supplies 44,46 (and/or pump 48) so as to apply voltages to theelectrodes 42 (and/or control the gas supply) to cause ions to be drivenor pulsed out of the ion trap, after they have been separated.

Although the present invention has been described with reference tovarious embodiments, it will be understood by those skilled in the artthat various changes in form and detail may be made without departingfrom the scope of the invention as set forth in the accompanying claims.

For example, although a stacked ring ion guide has been described asbeing used in the ion trap, other geometries of electrodes may be used.

Although a travelling wave has been described as the means by which ionsare extracted from the trap, alternative methods of releasing the ionsfrom the ion trap in a controlled manner may be used. For example, theaxial DC potential or pseudo-potential gradient may be ramped so as toforce ions out of the ion trap, or may be altered along differentlengths of the ion trap at different times so as to eject ions.

Although the spatial separation has been described as being achieved byusing opposing forces on the ions generated by pseudo-potential and anopposing DC potential, the spatial separation may be achieved by othermethods. For example, one of the opposing forces may be applied from agas flow instead of the DC potential or pseudo-potential gradient.

Although various values of the RF and DC voltages have been describedherein, these parameters and other operational parameters of the iontrap may be varied according to the desired mode of operation and/or theions trapped therein.

The ions may be caused to separate in the ion trap by ion mobilityinstead of mass to charge ratio, or by a combination of mass to chargeratio and ion mobility.

The ion trap of the various embodiments may be a discrete device or maybe an ion trapping region, e.g., within a larger device.

1. A method of filtering ions according to at least one physicochemicalproperty, comprising: trapping ions in an ion trap; and then spatiallyseparating the ions within the ion trap according to said at least onephysicochemical property so that ions become distributed within the iontrap according a known, determined or estimated physicochemical propertydistribution so that ions having different values of saidphysicochemical property are trapped in different regions of the iontrap; selecting a desired first value, or first range of values, of saidphysicochemical property for first ions desired to be ejected from theion trap; determining a first region of the ion trap in which said firstions are located from said known, determined or estimatedphysicochemical property distribution; and then driving or pulsing firstions trapped in said region out of the ion trap.
 2. The method of claim1, wherein ions trapped in the other of said different trapping regionsremain trapped in those regions during said driving or pulsing of saidfirst ions out of the ion trap.
 3. The method of claim 1 or 2,comprising selecting a desired value, or range of values, of saidphysicochemical property for second ions desired to be ejected from theion trap; determining a second different region of the ion trap in whichsaid second ions are located from said known, determined or estimatedphysicochemical property distribution; and then driving or pulsing thesecond ions trapped in said second region out of the ion trap.
 4. Themethod of claim 1, 2 or 3, wherein the ion trap comprises an elongatedion trapping volume, and wherein ions having said different values ofsaid physicochemical property are trapped in different regions along thelongitudinal axis of the ion trap.
 5. The method of any preceding claim,wherein the ions having said different values of said physicochemicalproperty are trapped in the ion trap at different distances from theexit of the ion trap prior to being driven out of the ion trap from saidexit.
 6. The method of any preceding claim, wherein the ion trap has alongitudinal axis and wherein said region from which the ions are drivenor pulsed out of is not a region adjacent an exit at a longitudinal endof the ion trap.
 7. The method of any preceding claim, wherein the ionsare spatially separated within the ion trap according to the at leastone physicochemical property so that the ions are dispersed along theion trap according to their physicochemical property values without thespatially separated trapped ions being separated by potential barriers.8. The method of any preceding claim, wherein said step of spatiallyseparating the ions comprises applying a first force to the ions withinthe ion trap in a first direction, said force having a magnitude that isdependent upon the value of said at least one physicochemical propertyof the ions; and applying a second force on these ions in the oppositedirection; optionally wherein the magnitude of said second force is notdependent upon the value of said at least one physicochemical propertyof the ions.
 9. The method of claim 8, wherein said ion trap comprisesone or more electrodes and said method comprises generating said firstforce by applying AC or RF potentials to said electrodes so as togenerate a pseudo-potential electric field that urges ions in the firstdirection.
 10. The method of claim 8 or 9, wherein said ion trapcomprises one or more electrodes and said method comprises generatingsaid second force by applying one or more DC potentials to said one ormore electrodes so as to generate a DC voltage or DC voltage gradientthat urges ions in the second direction; and/or wherein a gas flow isprovided through the ion trap so as to generate said second force. 11.The method of any preceding claim, wherein said step of driving orpulsing trapped ions out of a region of the ion trap comprises varyingan electrical potential along the trapping region that ions are beingdriven or pulsed out of, and/or travelling an electric potential alongat least a portion of the ion trap so as to drive the ions out of theion trap.
 12. The method of any preceding claim, comprising varying theelectrical potential profile along the first region when driving orpulsing ions out of the first region and/or varying the electricalpotential profile along a second different region when driving orpulsing ions out of the second region.
 13. The method of any precedingclaim, wherein ions of interest having the selected value, or range ofvalues, of said physicochemical property are ejected from the ion trapand transmitted to an ion analyser, or ion storage device.
 14. Themethod of any preceding claim, wherein unwanted ions having a value, orrange of values, of said physicochemical property that are not ofinterest are ejected or released from the ion trap and/or are discardedor neutralised.
 15. The method of any preceding claim, wherein the iontrap is an elongated ion trap and the step of ejecting ions from atleast some of said different regions of the ion trap is performed byaxially ejecting the ions from said at least some of said differentregions; or wherein the ion trap is an elongated ion trap and the stepof ejecting ions from at least some of said different regions of the iontrap is performed by radially ejecting the ions from said at least someof said different regions.
 16. The method of any preceding claim,wherein the at least one physicochemical property is mass to chargeratio and/or ion mobility.
 17. A method of mass spectrometry or ionmobility spectrometry comprising filtering ions according to the methodof any preceding claim; and mass analysing or ion mobility analysingions driven or pulsed out of the ion trap.
 18. An ion filter forfiltering ions according to at least one physicochemical property,comprising: an ion trap for trapping ions; an ion separator forspatially separating the ions within the ion trap according to at leastone physicochemical property; an ion driving or pulsing device fordriving or pulsing ions out of the ion trap; and a controller having aprocessor and electronic circuitry adapted and configured to: controlthe ion trap so as to trap ions therein; control the ion separator so asto spatially separate the ions within the ion trap according to said atleast one physicochemical property so that ions become distributedwithin the ion trap according a selected physicochemical propertydistribution so that ions having different values of saidphysicochemical property are trapped in different regions of the iontrap; determine a first region of the ion trap in which ions having apreselected first value, or first range of values, of saidphysicochemical property are located based on said physicochemicalproperty distribution; and then drive or pulse first ions trapped insaid region out of the ion trap.
 19. A mass spectrometer or ion mobilityspectrometer comprising an ion filter as claimed in claim 18, and adetector for detecting ions driven or pulsed out of the ion trap.
 20. Amass spectrometer or ion mobility spectrometer comprising an ion filteras claimed in claim 18, and a mass analyser or ion mobility analyser foranalysing ions driven or pulsed out of the ion trap.
 21. A method offiltering ions according to at least one physicochemical property,comprising: trapping ions in an ion trap; spatially separating the ionswithin the ion trap according to said at least one physicochemicalproperty so that ions having different values of said physicochemicalproperty are trapped in different regions of the ion trap; and thendriving ions trapped in one of said different regions out of the iontrap, optionally wherein ions trapped in only one of said differentregions are driven out of the ion trap at any one time.
 22. An ionfilter for filtering ions according to at least one physicochemicalproperty, comprising: an ion trap; an ion separator; an ion drivingdevice; and a controller configured to control the ion trap to trap ionstherein; control the ion separator so as to spatially separate the ionswithin the ion trap according to said at least one physicochemicalproperty so that ions having different values of said physicochemicalproperty are trapped in different regions of the ion trap; and then tocontrol the ion driving device so as to drive ions trapped in only oneof said different regions out of the ion trap at any one time.
 23. Amethod of ion mobility spectrometry and/or mass spectrometry comprising:trapping ions in an ion trap; spatially separating the ions within theion trap according to at least one physicochemical property; pulsing theseparated ions out of the ion trap and into an ion mobility separator,wherein ions that have been separated from each other in the spatiallyseparating step are pulsed out of the ion trap and into the ion mobilityseparator in the same ion pulse; and separating the ions pulsed into theion mobility separator according to ion mobility.
 24. The method ofclaim 23, wherein the step of pulsing the ions out of the ion trapcomprises pulsing all ions out of the trap in a single pulse.
 25. Themethod of claim 23 or 24, wherein said step of spatially separating theions causes ions having different values of said physicochemicalproperty, or different ranges of values of said physicochemicalproperty, to be trapped at different locations within the ion trap;and/or wherein ions having different values of said physicochemicalproperty, or different ranges of values of said physicochemicalproperty, are pulsed out of the ion trap from different locations withinthe ion trap during said pulsing step.
 26. The method of any precedingclaim, wherein the ion trap comprises a linear ion trap or wherein theion trap is elongated; and wherein ions are spatially separated alongthe longitudinal axis of the ion trap during the step of spatiallyseparating the ions.
 27. The method of any preceding claim, comprisingspatially separating the ions after all of the ions to be pulsed intothe ion mobility separator in said pulse have been accumulated; orspatially separating the ions whilst the ions are being accumulated inthe ion trap.
 28. The method of any preceding claim, wherein the atleast one physicochemical property is mass to charge ratio and/or ionmobility.
 29. The method of any preceding claim, wherein the methodcomprises performing a plurality of cycles of operation, wherein eachcycle comprises the steps of: (i) receiving and trapping ions in the iontrap; (ii) spatially separating the ions according to the at least onephysicochemical property within the ion trap; and (iii) pulsing the ionsout of the ion trap and into an ion mobility separator, wherein ionsthat have been separated from each other in step (ii) are pulsed out ofthe ion trap and into the ion mobility separator in the same ion pulse.30. The method of any preceding claim, wherein said step of spatiallyseparating the ions comprises applying a first force on the ions withinthe ion trap in a first direction, said force having a magnitude that isdependent upon the value of said at least one physicochemical propertyof the ions; and applying a second force on these ions in the oppositedirection; optionally wherein the magnitude of said second force is notdependent upon the value of said at least one physicochemical propertyof the ions.
 31. The method of claim 30, wherein said first and secondforces are counterbalanced at different locations within the ion trapfor ions having different physicochemical property values, such thatdifferent ions are trapped at said different locations.
 32. The methodof claim 30 or 31, wherein said ion trap comprises a plurality ofelectrodes and said method comprises generating said first force byapplying AC or RF potentials to said electrodes so as to generate apseudo-potential electric field that urges ions in the first direction.33. The method of claim 30, 31, or 32, wherein said ion trap comprisesone or more electrodes and said method comprises generating said secondforce by applying one or more DC potentials to said one or moreelectrodes so as to generate a DC voltage or DC voltage gradient thaturges ions in the second direction; and/or wherein a gas flow isprovided through the ion trap so as to generate said second force. 34.The method of any preceding claim, comprising travelling an electricpotential along the ion mobility separator so as to drive ions out ofthe ion trap and into the ion mobility separator during said pulsingstep, optionally wherein the electric potential is travelled along theion trap at a constant speed.
 35. An ion mobility spectrometer and/ormass spectrometer comprising: an ion trap for trapping ions; a spatialseparator for spatially separating the ions within the ion trap; an ionmobility separator for separating ions according to their ion mobility;a pulsing device for pulsing ions out of the ion trap; and a controllerarranged and adapted to control the spectrometer to: operate the spatialseparator so as to separate the ions within the ion trap according to atleast one physicochemical property; pulse the separated ions out of theion trap and into the ion mobility separator, such that the ions thathave been separated from each other are pulsed out of the ion trap andinto the ion mobility separator in the same ion pulse; and separate theions in the ion mobility separator.
 36. The spectrometer of claim 35,wherein the ion trap is a linear ion trap or an elongated ion trap; andwherein the controller is arranged and adapted to cause ions to bespatially separated along the longitudinal axis of the ion trap.
 37. Aspectrometer arranged and adapted to perform the method of any one ofclaims 23-34.
 38. A method of mass spectrometry and/or ion mobilityspectrometry comprising: trapping ions in an ion trap; and thenspatially separating the ions within the ion trap according to at leastone physicochemical property so that ions having different values ofsaid physicochemical property are trapped in different regions of theion trap; and then driving or pulsing first trapped ions out of a firstregion of the ion trap and into a discontinuous ion analyser at a firsttime, whilst retaining other ions trapped in the ion trap; analysingsaid first ions in a first cycle of said discontinuous ion analyser;driving or pulsing second trapped ions out of a second, different regionof the ion trap and into the discontinuous ion analyser at a second,subsequent time; and analysing said second ions in a different cycle ofsaid discontinuous ion analyser.
 39. The method of claim 38, wherein theions are spatially separated within the ion trap according to the atleast one physicochemical property so that the ions are dispersed alongthe ion trap according to their physicochemical property values withoutthe spatially separated trapped ions being separated by potentialbarriers.
 40. The method of claim 38 or 39, wherein whilst the firsttrapped ions are driven or pulsed out of the first region of the iontrap, the second trapped ions are caused to remain in said second regionuntil the second trapped ions are driven or pulsed out of the secondregion into the discontinuous ion analyser at the second time.
 41. Themethod of claim 38, 39, or 40, wherein the ion trap comprises anelongated ion trapping volume, and wherein ions having said differentvalues of said physicochemical property are trapped in different regionsalong the longitudinal axis of the ion trap; and/or wherein the ionshaving said different values of said physicochemical property aretrapped in the ion trap at different distances from an entrance to theion analyser prior to being driven out of the ion trap.
 42. The methodof any preceding claim, wherein said step of spatially separating theions comprises applying a first force on the ions within the ion trap ina first direction, said force having a magnitude that is dependent uponthe value of said at least one physicochemical property of the ions; andapplying a second force on these ions in the opposite direction;optionally wherein the magnitude of said second force is not dependentupon the value of said at least one physicochemical property of theions.
 43. The method of claim 42, wherein said first and second forcesare counterbalanced at different locations within the ion trap for ionshaving different physicochemical property values, such that differentions are trapped at said different regions.
 44. The method of claim 42or 43, wherein said ion trap comprises one or more electrodes and saidmethod comprises generating said first force by applying AC or RFpotentials to said electrodes so as to generate a pseudo-potentialelectric field that urges ions in the first direction.
 45. The method ofclaim 42, 43, or 44, wherein said ion trap comprises one or moreelectrodes and said method comprises generating said second force byapplying one or more DC potentials to said one or more electrodes so asto generate a DC voltage or DC voltage gradient that urges ions in thesecond direction; and/or wherein a gas flow is provided through the iontrap so as to generate said second force.
 46. The method of any one ofclaims 38-45, wherein each of the steps of driving or pulsing trappedions out of a region of the ion trap and into a discontinuous ionanalyser, whilst retaining other ions trapped in the ion trap, comprisestravelling an electric potential along at least a portion of the iontrap so as to drive the ions out of the ion trap.
 47. The method ofclaim 46, wherein said electric potential is travelled along a firstlength of the ion trap in order to drive said first ions out of the iontrap, and said electric potential is subsequently travelled along asecond, different length of the ion trap in order to drive said secondions out of the ion trap.
 48. The method of claim 47, wherein the firstlength extends from a first location in the ion trap to the exit of theion trap, whereas the second length extends from a second location inthe ion trap to the exit of the ion trap, wherein the second location isfurther from the exit than the first location.
 49. The method of claim46, 47 or 48, wherein the electric potential that is travelled along theion guide is a DC potential barrier or well.
 50. The method of any oneof claims 38-49, wherein said discontinuous ion analyser is a time offlight mass analyser, or a pulsed ion mobility analyser.
 51. The methodof any one of claims 38-50, wherein substantially all of the ions drivenout of the ion trap from any given trapping region are analysed in asingle cycle of the discontinuous ion analyser.
 52. A mass spectrometerand/or ion mobility spectrometer comprising: an ion trap; an ionseparator device; an ion driving device; a discontinuous ion analyser;and a controller arranged and configured to: trap ions within the iontrap; control the ion separator device so as to spatially separate theions within the ion trap according to at least one physicochemicalproperty so that ions having different values for said physicochemicalproperty are trapped in different regions of the ion trap; and thencontrol the ion driving device so as to drive or pulse first trappedions out of a first region of the ion trap and into the discontinuousion analyser at a first time, whilst retaining other ions trapped in theion trap; control the discontinuous ion analyser so as to analyse saidfirst ions in a first cycle of analysis; control the ion driving deviceso as to drive or pulse second trapped ions out of a second, differentregion of the ion trap and into the discontinuous ion analyser at asecond, subsequent time; and control the discontinuous ion analyser soas to analyse said second ions in a second cycle of said analysis. 53.An ion trap for spatially separating ions according to a physicochemicalproperty, wherein the ion trap comprises: a plurality of electrodes; atleast one AC or RF voltage supply; at least one DC voltage supply and/ora pump for pumping gas through the ion trap; and a controller andcircuitry arranged and configured to: control the at least one AC or RFvoltage supply so as to apply one or more AC or RF voltages to saidelectrodes so as to generate a pseudo-potential electric field thaturges ions in a first direction; control the at least one DC voltagesupply so as to apply one or more DC voltages to said electrodes so asto generate a DC electric field that urges ions in a second directionopposite to the first direction, and/or control the pump so as pump gasthrough the ion trap so as to urge ions in a second direction oppositeto the first direction; control the DC voltage supply and/or pump and/orAC/RF voltage supply so as to pulse or drive ions out of one or moreregions of the ion trap.
 54. The ion trap of claim 53, wherein the iontrap comprises an elongated ion trapping volume; and wherein in use ionshaving different values of said physicochemical property are trapped indifferent regions along the longitudinal axis of the ion trap, and/orwherein ions having different values of said physicochemical propertyare trapped in the ion trap at different distances from an exit of theion trap.
 55. The ion trap of claim 53 or 54, wherein the ion trap has alongitudinal axis and wherein said one or more regions from which theions are driven or pulsed from is not a region adjacent an exit at alongitudinal end of the ion trap.
 56. The ion trap of claim 53, 54 or55, wherein the ions are spatially separated within the ion trapaccording to the physicochemical property so that the ions are dispersedalong the ion trap according to their physicochemical property valueswithout the spatially separated trapped ions being separated bypotential barriers.
 57. A method comprising: trapping ions in an iontrap; applying a first force on the ions within the ion trap in a firstdirection, said force having a magnitude that is dependent upon thevalue of a physicochemical property of the ions; applying a second forceon these ions in the opposite direction so that the ions separateaccording to the physicochemical property value as a result of the firstand second forces; and then pulsing or driving ions out of one or moreregions of the ion trap.
 58. The method of claim 57, wherein themagnitude of said second force is not dependent upon the value of saidat least one physicochemical property of the ions.
 59. The method ofclaim 57 or 58, wherein said ion trap comprises one or more electrodesand said method comprises generating said first force by applying AC orRF potentials to said electrodes so as to generate a pseudo-potentialelectric field that urges ions in the first direction.
 60. The method ofclaim 57, 58 or 59, wherein said ion trap comprises one or moreelectrodes and said method comprises generating said second force byapplying one or more DC potentials to said one or more electrodes so asto generate a DC voltage or DC voltage gradient that urges ions in thesecond direction; and/or wherein a gas flow is provided through the iontrap so as to generate said second force.
 61. The method of any one ofclaims 57-60, wherein said step of driving or pulsing trapped ions outof a region of the ion trap comprises varying an electrical potentialalong the trapping region that ions are being driven or pulsed out of,and/or travelling an electric potential along at least a portion of theion trap so as to drive the ions out of the ion trap.
 62. The method ofany one of claims 57-61, comprising varying the electrical potentialprofile along a first region of the ion trap when driving or pulsingions out of the first region and/or varying the electrical potentialprofile along a second different region of the ion trap when driving orpulsing ions out of the second region.
 63. The method of any one ofclaims 57-62, wherein the ion trap is an elongated ion trap and the stepof ejecting ions from at least some of said different regions of the iontrap is performed by axially ejecting the ions from said at least someof said different regions; or wherein the ion trap is an elongated iontrap and the step of ejecting ions from at least some of said differentregions of the ion trap is performed by radially ejecting the ions fromsaid at least some of said different regions.
 64. The method of any oneof claims 53-63, wherein the at least one physicochemical property ismass to charge ratio and/or ion mobility.
 65. The method, spectrometeror ion trap of any preceding claim, wherein the ions of differentphysicochemical property values are spatially separated over a length of≥x mm within the ion trap, wherein x is selected from the groupconsisting of: 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12,14, 16, 18, 20, 25, 30, 35, 40, 45 and
 50. 66. The method, spectrometeror ion trap of any preceding claim, wherein ions having any given valuefor said physicochemical property are distributed over ≤y mm within theion trap, wherein y is selected from the group consisting of: 0.5, 0.6,0.7, 0.8, 0.9, 1, 1.2, 14.4, 1.6, 1.8, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7,8, and
 9. 67. The method, spectrometer or ion trap of any precedingclaim, wherein the physicochemical property value is mass to chargeratio; wherein the ions are separated such that they are dispersed overa length L in the ion trap; and wherein the ratio of the range of massto charge ratios, in Daltons, trapped in the ion trap over length L tothe length L over which the ions are trapped, in mm, is selected fromthe group consisting of: (i) 5-6; (ii) 6-7; (iii) 7-8; (iv) 8-9; (v)9-10; (vi) 10-11; (vii) 11-12; (viii) 12-13; (ix) 13-14; (x) 14-15; (xi)15-16; (xii) 16-17; (xiii) 17-18; (xiv) 18-19; and (xv) 19-20.
 68. Themethod, spectrometer or ion trap of any preceding claim, wherein theseparation of the ions according to said physicochemical property ispreserved during ejection of the ions from the ion trap.